Thursday, October 26, 2017

Simple Ain’t So Simple Anymore

Biology Concepts – prokaryotes, simplicity, complexity, organelles, microcompartments

Not everything new is better; new doesn’t
necessarily mean improved. Remember the
“New” Coke debacle?
Newer is better, right? Everything old is simple and plain. Back in the good old days, you had to read a book, but today you can browse the internet and pick from 8000 songs while you drive to the superstore to pick up a Kindle. Today is faster. Better. More complex?

How about living in 1800. Could you catch and kill your dinner with a trap of your own making, followed by gutting and dressing it on the back porch of a house you built with your own hands, while you try to keep your entire family from being eaten or dying from an infected scratch?  Now whose world seems complex!

This same belief has been applied to forms of life. Bacteria are old and simple; we are new and complex. Plants and animals can do millions of things that bacteria can’t, because they are so simple and primitive and we are so high tech, biologically speaking.

But it is a mistake to call bacteria simple or primitive. They may not have all the bells and whistles that eukaryotic (eu - true and karyo = nucleus) cells have, but they have survived much longer than other life forms, and they outnumber us by billions. There are more bacteria in a handful of rich soil than people who have ever lived on Earth. So don’t confuse complexity with success.

A cursory look at bacteria would suggest that they are indeed simple. They are bags of chemicals, without the complex organelles that mark eukaryotic cells. Plus, they're small; the whole organism is just one cell. They have just one chromosome and fewer genes than eukaryotic cells. It would be easy to see them as simple.

Even at the biochemical level prokaryotes (pro = primitive) appear simple compared to eukaryotic cells. Our more modern cells aren’t satisfied with just making more proteins, they also modify many of these proteins, adding carbohydrates, acetyl groups, phosphate groups, sulfur groups, etc. These post-translational modifications (after peptides are translated from mRNA messages) are crucial for different functions and for interactions with messengers and DNA.

Histones are protein complexes that help DNA to coil up into tight 
configurations. But DNA it is tightly packaged, it is hard for 
individual genes to be transcribed and made into protein. Histone 
acetyltransferases are enzymes that add acetyl groups to the histones 
and open DNA to be read. Histone deacteylases do the 
opposite, they add acetyl groups and cause the DNA 
to tightly coil.
The exception here is that less than a decade ago scientists found that many prokaryotes also do some kinds of post-translational modifications, includingphosphorylation and acetylation. Acetylation, the addition of a -COCH3 group to a molecule, is important in eukaryotic cells for several reasons, not the least of which is in determining which DNA is open to be replicated or transcribed (copied to mRNA).

Data from 2004 was the first to show that prokaryotes can carry out phosphorylation (addition of PO3 groups) to proteins. What is more, acetylation and phosphorylation are reversible modifications, so an additional layer of complexity is added. Prokaryotic proteins have one function when modified and another when not modified, just like modification of eukaryotic proteins. Sounds like prokaryotes have more going on than we thought.

Prokaryotes are the real success stories of life on Earth. They can do things some things eukaryotes can’t do (more on this next time). Even more amazing, every deficit we have said they have - they can’t do this, they don’t have those – can be seen as a reason they are more amazing.

Prokaryotes are single celled organisms, so they have less specialization. But this means that the cell has to carry out every function that the organism needs. Could your fat cells produce antibodies and kill off protozoan invaders? I think not. We also poke fun at prokaryotes because they don’t have organelles; but this means they have to find a way to do all their chemistry in one big open environment, much more difficult .……….or maybe not.

That classic rule of biology, "eukaryotic cells have organelles and prokaryotic cells don’t," may not be completely true. This would be a big exception.  Evidence shows that many kinds of prokaryotes do have local environments, called microcompartments. We have all been living a lie!

The most studied of the microcompartments is the carboxysome. This hollow shell, first described as far back as 1956, holds enzymes (RuBisCo, see When Amazing Isn’t Enough) that many prokaryotes use for carbon fixation. Photosynthesis is the most obvious type of carbon fixation, where carbon in a gas form (CO2) is converted to carbon in an organic, solid form (carbohydrates).

Carboxysomes as seen by electron microscopy. They really
do look geometric. The faces and corners are specific groups
of proteins, and hold the enzymes inside the microcompartment.
There are minute pores where the proteins come together
to let reagents and products move in and out of the carboxysome.
RuBisCo is a fairly inefficient enzyme, so sequestering it with its substrate inside a microcompartment works to increase the production of energy. Doesn’t this sound a lot like one of the key reasons for the development of organelles – the bringing together of reagents for increased efficiency of reactions?

But it is not just photosynthetic bacteria (cyanobacteria) that use carboxysomes. Many other autotrophic bacteria (auto = own and troph = food) use carboxysomes to fix carbon during chemosynthesis. Chemoautotrophs, for instance, are organisms that use chemical energy rather than sunlight energy to fix carbon.

In many prokaryotes, the oxidation of hydrogen sulfide or ammonia (a nitrogen containing compound) provides the energy for producing organic carbon; Thiomargarita namibinesis from our posts on giant bacteria uses sulfur for chemosynthesis. But there are also organisms that use the energy from the production of methane to drive carbon fixation. You have undoubtedly had experience with intestinal prokaryotes that produce methane gas (methanogens) – don’t try to say you haven’t.

The carboxysome (as a model of many microcompartments) is not a membrane bound bag as organelles are in eukaryotes. Carboxysomes are more like soccer balls made of protein, but in this case they hold a rigid polyhedral form and don’t get bicycle kicked into a prokaryotic net by Pele.

Each face of the shell is made up of a two dimensional polymer of protein hexagons. However, as architects will tell you, this is a difficult shape to close using only hexagons, even with 10,000 of them, like the typical carboxysome has. Soccer balls and the dome at the Epcot Center use strategically placed pentagonal faces that allow for the turning of the hexagonal faces and a closing of the compartment (see cartoon above).

These are cartoons showing the structure of a
carbon fullerene (right) and a carbon nanotube
(left). Each green sphere represents a carbon atom.
These structures are very strong, like for making
bicycle helmets. They may also become useful for
things like space elevators, nanoelectrical circuits,
and solid lubricants.
We have used this hexagonal and pentagonal combination for decades, but it was identified in bacteria less than five years ago. This arrangement is also seen in viral protein coats, as well as in carbon fullerenes, which are superstable carbon nanostructures described in 1985 and named for the inventor of the geodesic dome, Buckminster Fuller.

Could this be the exception – nature stealing an idea from humans? Probably not, I’m guessing Dr. Fuller independently happened upon the same solution that nature had worked out millions of years ago – but it took a heck of an intellect to recognize a good thing.

It might be lucky for us that Fuller’s domes had us looking for this combination in other areas. Carboxysomes are present in up to 25% prokaryotic pathogens (disease causing organisms), and current research is aiming to disrupt the formation of the hexagonal/pentagonal compartments as a way to kill, or at least slow down, the microbes. So many prokaryotic pathogens are developing resistance to traditional antibiotics that a new approach will be heartily welcomed.

There are other microcompartments besides the carboxysome. The bacterium Clostridium kluyveri is proposed to have a metabolosome compartment for the conversion of ethanol into carbohydrates. Furthermore, Salmonella enterica, is capable of producing two different metabolosomes; one for propane-1,2-diol and one for ethanolamine, for conversion of these substrates into energy-containing carbon sources.

The evidence of these additional microcompartments makes one wonder just how many different species of protein shelled microcompartments there may be. To investigate this question, a group from UCLA recently published a study using comparative genomics (comparing genes of similar and dissimilar organisms to find groups of genes of similar function) to point out possible enzyme pathways that may be sequestered in microcompartments.

Their late 2012 study suggests that new types of microcompartments for different types of propanediol metabolism, and the identification of microcompartments in organisms for which they were previously unknown, like mycobacteria. The genomic evidence also suggests new types of protein shells, differing compartments being used for differing variants of enzyme function.

It is in these final examples that we see a more concrete purpose for the microcompartment. During the metabolism of alcohol, propane-1,2-diol, or ethanolamine, a compound called acetaldehyde is formed. This is a toxic product that needs to be converted to acetic acid in rapid order to avoid toxicity to the cell. By isolating the acetaldehyde in the metabolosome, S. enterica improves its own living conditions. This is also important to us humans.

This is not a before and after picture for an embarrassing
karaoke incident. This is a demonstration of the facial
flushing reaction when a person has an ALDH2 mutation, and 
can’t metabolize alcohol efficiently.
Many Asians and Ashkenazi Jews have a mutation of the acetaldehyde dehydrogenase (ALDH2) gene that produces the enzyme that rids the body of acetaldehyde after the consumption of alcohol. The mutation produces a poorly functioning enzyme, so acetaldehyde builds up in their systems and causes a facial flushing reaction. If both ALDH2 genes (one from mom, one from dad) are mutated, the person gets violently ill from consuming ethanol. As you might imagine, populations in which this mutation is prevalent have very low rates of alcoholism.

So we have the exception that prokaryotes are not really without organelles; theirs just look different. Could you guess that the exception goes the other way too? Well, it does. The nucleus of eukaryotic cells works with microcompartments that allow certain things in and out, but keep your DNA inside the nucleus.

The pores of the nucleus (Cells Are Great Multitaskers) are complex openings made up of many proteins. Why? Nuclei could just use receptors to allows certain things in or out, similar to the system used by the cell plasma membrane. But evolution went with a more complex solution.

The vault complex is made of 78 identical protein chains.
One chain is shown in white. Together, they form a
microcompartment that is crucial for our nucleus function.
There is a protein microcompartment called a vault complex that works with the pore complex. This is a highly regulated way of moving RNAs and ribosomes (made in the nucleolus which is inside the nucleus) out of the nucleus, while keeping your DNA inside. I don’t think it is a hard concept to grasp that you cells are happier when your DNA stays inside the nucleus; do you keep your valuables on your front lawn?

Next time we will see how the nucleus, its pore complex, and its microcompartment carriers helped us make the jump from prokaryote to eukaryote. The nucleus is a later evolutionary development, but it still uses a prokaryotic system. This is clue that helps us investigate our cellular family tree. 

Jorda, J., Lopez, D., Wheatley, N., & Yeates, T. (2012). Using comparative genomics to uncover new kinds of protein-based metabolic organelles in bacteria Protein Science DOI: 10.1002/pro.2196

For more information or classroom activities on bacterial microcomponents, post-translational modification of proteins, alcohol metabolism, or the vault complex, see:

Bacterial microcomponents –

Protein post-translational modification –

Alcohol metabolism –

Nuclear vault complex –

Thursday, October 19, 2017

Cell To Cell Tanning

Biology Concepts – vacuoles, phagocytosis, melanin, cephalopod camouflage

Sometimes, the name of an item becomes the same
as its function. Have you ever asked for a Puff when you
needed a facial tissue? But we all ask for a Kleenex.
Vacuoles are the same, but in reverse, they are all
very similar, but are named based on their function.
Last week we discussed the specific characteristics of organelles that allow them and the cells in which they work to specialize their activities. But being specific is not always more accurate. We ask for a Kleenex no matter what brand of facial tissue is handy. Many people ask for a Coke, when they really mean any soda at all.

There is an organelle that gets the same treatment. The vacuole is a generic membrane bound compartment; its function and name brand is usually defined by what it is carrying. Lysosomes are vacuoles, named for the lysosomal enzymes they carry. Peroxisomes are vacuoles, named for the peroxidase enzymes they carry. Branding can be important, even in biology.

The vacuole is a membrane bound compartment inside
the cell. The central vacuole of the plant cell is shown above,
and can occupy a huge percentage of the cell volume. It can
store water or carbohydrates, and can change size very rapidly.
Most cell types have many vacuoles or vesicles (small vacuoles), but there are exceptions. Plant cells generally just have one vacuole - not one type - but a total number of 1. This is called the central vacuole, and can occupy up to 90% of the cell volume. We have discussed its functions several times; the central vacuole is the part of the cell that fills and empties in order to induce movement of plant components, like flowers blooming and leaves folding (Plants That Don’t Sleep). Vacuole functions seem to be quite varied, from digestion to structure.

The melanosome is another type of vacuole. Take a guess how it got its name…… O.K., it’s because it carries melanin. Melanin (melas in Greek means black) is the pigment that gives color to your skin, hair, iris (the colored part of your eye), and even parts of your brain.  One crucial function of melanin is to protect your skin cells from ultraviolet (UV) damage. This is why natives in sunnier areas have darker skin, while people from latitudes farther north and south have lighter skin tones.

Inuit (translated as “the people”) are a group of different
peoples of the north latitudes. In Alaska, the term Eskimo is
often used because its meaning includes the two main groups
that live there. All Inuit seem to have darker skin tones than one
would think was called for.
However, even in this there is an exception. Inuit natives in the Arctic have darker skin on average as compared to white Americans or Europeans. This may be because the amount of sunlight that reflects off the snow increases their UV exposure, or because they have been living in this environment for only 5000 years and haven’t had time to adopt a lighter skin color. Either way, you don’t see many red-headed, freckled, Inuits.

In your skin, melanin is produced by a specialized skin cell type called the melanocyte. We discussed in last week’s post that the different combinations of organelles allows cells to take on specialized function, and this is the case with melanocytes. Melanin is synthesized from the amino acid tyrosine within the melanosome, and remains stored in this organelle when it is stored, moved, and when it performs it jobs.

Only 5-10% of skin cells are melanocytes, and they are located only in the deepest  layer of skin, called the stratum basale. (stratum = layer and basale = base or lowest) But if you look at dark skin or at a well-tanned person, it seems that there is pigment all over. You would think that freckles would be more natural, the melanocytes that produce melanin are spotted over the skin, and so are freckles. So how does a person get tanned skin evenly, or how is it that dark complexions are homogeneous over a large area?

This is where the melanosomes as organelles are so exceptional; they can move from melanocytes to keratinocytes (skin cells). This is unique amongst organelles and is still not fully understood. However, much evidence has been uncovered in just the past few years.

Melanocytes are rare in the skin, but can project up into the
upper layers of the skin in order to spread out their melanin.
The melanocyte is stimulated to make melanin due to UV exposure of keratinocytes. When the DNA of the skin cell is hit with UV radiation, it triggers production of a hormone called alpha-melanocyte stimulating hormone, alpha-MSH. This hormone acts on the melanocytes through receptors on the cell membrane (2nd messenger system, see Multitaskers). The message is transferred to the melanocyte nucleus and melanin is produced in melanosomes.

Next, the melanosome grows dendrites (from Greek for tree), sometimes called filipodia (like a foot). These extensions snake their way between keratinocytes and reach up into the higher layers of skin cells. The dendrites are rich in melanosomes, but research has yet to show if the melanosomes are responsible for the formation of the dendrites. This may be so, because it is not until the keratinocytes acquire melanosomes that they also start to form these filopodia.

The melanosomes end up inside the skin cells, and this is where current research is focused. Recent hypotheses for their movement include ideas that they are released from melanocytes and then taken up by keratinocytes, or that there is fusion of the keratinocyte and the melanocyte.

However, evidence from a 2010 study indicates that the keratinocyte actually swallows (phagocytoses, phag = eat and cyto = cell) the ends of the dendrites, and the included melanosomes become skin cell organelles. The keratinocyte membrane expands around the end of the dendrite, then pinches together until the two sides meet each other. Part of the melanocyte, its cytoplasm, its membrane, and its melanosomes ends up as part of the keratinocyte. Your trip to the beach causes your cells to eat each other, cool!

The phagocytosed melanosomes can have two fates, but neither is what you would expect. Usually phagocytosed vacuoles are merged with lysosomes and the contents are degraded. But not so for the melanosome.

Some are pushed out into new keratinocyte filopodia. These dendrites can then be phagocytosed by other keratinocytes. In this way, the melanin produced by the few melanocytes can be spread through out the layers and surface area of the skin cells and result in a continuous skin tone. However, if you have fewer melanocytes, or they have a mutated alpha-MSH receptor that forces them to produce more local melanin, you end up with freckles.

These micrographs show that melanosomes aggregate around
the nucleus of keratinocytes that have been exposed to UV
radiation in order to protect the DNA in the nucleus.
The second fate for the melanosomes occurs when they get the right signal, and is just as amazing. The UV rays that can stimulate the DNA to make alpha-MSH can also induce DNA damage; this is the main reason for melanin production. In response to increased sun exposure, the keratinocytes that take up the melanosomes will move them into position between the UV source and their DNA, like a hat worn by the nucleus. There the melanin absorbs the radiation like nature’s own sunscreen.

In truth, melanin is really three different pigments. Eumelanin (eu = true) is dark brown and is the most common type of melanin. But the same cells and melanosomes also produce pheomelanin (pheo = dusky) which is more reddish in color. Pheomelanin is responsible for red hair and for the freckle color in fair-skinned individuals.

Finally, there is neuromelanin in the brain, which gives a dark color to the portions of the brain like the substantia nigra (Latin for black substance). This brain structure coordinates muscle movement, and when these cells die or malfunction, the result is Parkinson’s disease. The melanin in these cells is actually just a byproduct of dopamine production. Parkinson’s disease can be treated, at least in its early stages, with synthetic dopamine.

Although it serves no known function in the midbrain, melanin does help in ways other than UV absorption. Different stressors, like chemicals, oxidative damage, and high temperature are also suppressed by melanin.

Melanin is particularly important for cephalopods, like squid, cuttlefish, and octopuses (yes, the plural of octopus is octopuses or octopodes, not octopi). These animals can disguise themselves within their environments and this task requires melanin. Under their skin, cephalopods have three or four layers of cells that allow them to create many colors and surface characteristics.

Chromatophores are the top level. The have saccules of melanin that can change shape. When stretched out, they show much color, but when relaxed, only pinpoints of color show. Each saccule is attached to many muscles and each muscle is innervated by several neurons; the octopus has fine control of each and every saccule, and each saccule can rapidly assume a different size and shape. This makes many shades and patterns possible

Cephalopods use several specialized cell types to hide
themselves from predators or to display for a mate or
rival. These special functions are possible, in part, because
of the organelles they possess. In the case of the blue ring
octopus, the blue is not from melanin, and is used to warn
of its toxicity, not to hide.
Below the chromatophores are the iridophores. These are like little mirrors that can also change angle position through many muscle and nerve controls. This allows the cephalopod to change the reflectivity and shine of its surface. Under this layer are the leucophores. They specialize in reflecting the dominant light wavelengths that they receive. These are the cells that help the octopus to match its surrounding colors so well (amazing video). Lastly, only some cephalopods have a layer of photophores that produce light (bioluminescence). We will talk about this amazing feat in a future series of posts.

Working together, and coordinated by their fantastic eyes, cephalopod skin cell layers can perform some amazing tricks to help the organism to survive. All this muscle control and sensory input requires a big brain, and cephalopods have the biggest brains of all the invertebrates (no backbone) and bigger than many vertebrates.  I think they should be worthy of a post or two in the future, especially since almost all cephalopods are color blind!

But back to melanin. Squid and octopus ink is also made of melanin, and is most often used to confuse predators, but I especially like its effect when used with eggs, water, and flour – try squid ink pasta sometime, you’ll like it.

Finally, there is a new way that melanin is helping science. Melanosomes are big, and they tend to fossilize well, so scientists are starting to learn what the coloration of dinosaurs might have been based on the preserved melanosomes and their included melanins.

We have looked at several organelle types, and have seen how they allow for specialized cell functions. But what if you had to get along without organelles, could a cell cope? We'll see about this next week.

Suman K. Singh, Robin Kurfurst, Carine Nizard, Sylvianne Schnebert, Eric Perrier and Desmond J. Tobin (2010). Melanin transfer in human skin cells is mediated by filopodia—a model for homotypic and heterotypic lysosome-related organelle transfer FASEB Journal DOI: 10.1096/fj.10-159046

For more information and classroom activities on vacuoles, melanin, melanosome movement, or cephalopod camouflage, see:

Vacuoles –

Melanin –

Melanosome movement –

Cephalopod camouflage –

Thursday, October 12, 2017

Cells Are Great Multitaskers

Biology concepts – compartmentalization, organelle function, cellular biochemistry

This chart represents a portion of the cellular reactions
that are taking place every second in a mammalian cell.
It looks more like a multicolored plate of pasta, but
shows you how complex a single cell is, and remember
that this doesn’t even count all the reactions for one cell
to be able to talk to another cell.
It is hard to estimate the number of reactions that must take place in a cell every second in order to keep a cell alive and performing its jobs(s)...... but I bet it is more than seven or eight.

The typical mammalian cell contains 2000 or more different proteins as well as many thousands of non-proteins (lipids, carbohydrates, and nucleic acids). Each molecule is crucial for carrying out chemical reactions, and each individual molecule is itself produced, modified, and destroyed by chemical reactions.

When I started to think about all this chemical activity, I looked to see if someone had counted, or at least estimated, the number of reactions taking place in the cell at any one time. I got no answer, not even a reliable guess from a credible source.

Think of it in this light, a plant cell has to perform more than twenty reactions to convert one photon of light into the chemical energy that will later be used for the synthesis of glucose. Each of these twenty reactions is occurring simultaneously at least hundreds of times in every chloroplast of the plant cell, and a single plant cell might have more than one hundred chloroplasts. The numbers add up fast, but remember that production of carbohydrate from light energy is just one of thousands of functions of a plant cell. There are chemical reactions occurring every second for all of these functions.

All this chemistry results in perhaps hundreds of thousands or millions of reactions each second, and all taking place within the confines of a cell that is too small to be seen with the naked eye. Wow!

When talking to students, I often use the analogy that a cell is like a factory, producing many different products at the same time. Not unlike a factory, a cell has to perform many functions, such as energy production, product manufacture, oversight and management, transportation of products, quality checks, and cleanup. What complicates matters is that all these different jobs have to be able to occur simultaneously.

I often use the analogy that a cell is like a factory, with
different departments. Other like the cell as a city
analogy. I even had one student make the analogy
that the cell is like a movie set, where the nucleus is
the director, and the plasma membrane is the fence
around the movie lot, etc.   She got an A.
How can a factory, or a cell for that matter, keep all the parts for all the different products, all the different workers, and all the different processes and jobs from messing each other up? A factory does this by setting up departments, where individual jobs take place, and then creating management teams that coordinate the work of the different departments—although to often there is too much management and too little production, but that is another matter.

The business and manufacturing industries stole this strategy from the cell, just as most our good ideas have been copied from nature. The cell uses compartments to increase the efficiency of all its needed chemical reactions. In eukaryotic (eu = true, and karyo= nucleus) cells, the compartments are called organelles (organ = instrument and elle = small), most of which are membrane bound containers.

Remember in our discussion of why cells must be small (It’s All In The Numbers) we said that mixing rate (time needed for a molecule to become evenly dispersed in a cell) and traffic time (time needed for two molecules needed for a certain reaction to find one another) are important for determining the maximum size of a cell.

Membrane bound organelles sequester needed components and create different local environments so that their mixing rates and traffic times are reduced. The result is a cell that is more efficient and can be bigger. This is evidenced by the fact that prokaryotic (pro = before) cells, such as bacteria, don’t have organelles and are about 50 times smaller than eukaryotic cells which have evolved organelles.

The nucleus has two membranes that form an envelope.
The outer membrane is continued as the endoplasmic
reticulum (ER), another vital cell organelle. The ribosome
attached to the ER, so it is easy to see how the organelles
work together to make a functioning cell.
The membranes of organelles look a lot like the membrane that surrounds the cell itself, but organelle membranes are often modified for their particular job. Take the nucleus (Welsh for "kernel of a nut," meaning the central part of a thing) for instance. It has two membranes and nuclear pores that run through both membranes are very specific for what they will let into and out of the nucleus.

The plasma membrane of the cell also limits the passage of molecules, but the nuclear pores are a complex of many unique proteins and this structure that is nowhere to be seen on the cell’s plasma membrane. Just like the membrane of the cell separates what is in the cell from what is outside the cell, the membrane of the organelle separates the needed components of their reactions from all the unneeded components of the cell.

In addition, many chemical reactions in organelles require the membrane as a workbench. Thousands of reactions take place in or across the membrane. This is an important function of many types of organelles, they increase the membrane surface area of a cell without making it bigger.

Some cellular reactions produce or use an intermediate molecule that must be separated across a membrane in order for the rest of the reaction to take place. This is the case for the mitochondrion – the energy producer in eukaryotic cells. To produce ATP (adenosine triphosphate, the chemical currency unit of energy in the cell), the mitochondrion sets up a gradient of protons between two membranes (remember that the nucleus has two membranes also) of the mitochondrion. The energy from the leaking of protons back into the inner space is used to produce ATP. We will talk more about these organelles with two membranes in an upcoming post.

Second messenger systems allow for messages from outside
the cell to be transmitted throughout the cell. There are three
general types, including one for gases like nitric oxide. In all,
there are more than two dozen different signal transduction
cascades, each with its own set of reactions.
Likewise, the outer membrane of the cell has many jobs that require messages to be transferred from one side of the membrane to the other. Called second messenger systems, these reactions are mechanisms to bring messages from outside the cell to the inside of the cell without the need for anything to cross the cell’s boundary.

In some cases, the membrane is not enough compartmentalization. The lysosome is an interesting organelle whose job is to break down many complexes that are brought into a cell and to recycle old organelles so the cell can reuse the parts. To do this, the lysosome contains proteins that can eat up other proteins, lipids, and carbohydrates. Unfortunately, these are the exact same molecules that make up the cell and the lysosomal membrane themselves. So why doesn’t the lysosome digest itself, and the entire cell for that matter?

The protein enzymes in the lysosome work efficiently within a narrow range of acid pH. Therefore, this organelle is acidified when produced. If the lysosome ruptures, the 7.2 pH of the cytoplasm will inactivate the lysosomal acid hydrolases, so the cell is protected. In addition, the lysosome membrane has many sugars stuck to it that act as a buffer between the lipids and proteins of the lysosomal membrane and lysosomal enzymes. There probably is some damage to the lysosome membrane, but repair reactions also help to keep the membrane intact. The cell often has redundant systems for safety.

So, we have seen that many of the organelles function to keep things sequestered in the cell, either for protection, organization, efficiency, or function. However, there are other reasons why organelles are a good idea.

Osteoclasts and osteoblasts are hard workers, so much so
that they needed more than one set of instructions for their
work. The osteoclast above shows multiple nuclei for many
DNA copies. Sometimes separate osteoblasts will join
together to form a multinucleated giant cell.
Organelles increase specificity, both for individual reactions and for cellular activity as a whole. Many cells in multicellular organisms are specialized for a certain function, and their organelles help them carry out this function. For instance, muscle cells are specialized for contraction, and this requires lots of energy. Therefore, they need many mitochondria, but few other types of organelles. These cells might contain 10-100 times more mitochondria than other cell types.

Likewise, osteoclasts (osteo = bone, clast = break) cells break down bone – and yes, you are breaking down and rebuilding your bones every second of every day. This activity requires many proteins to be produced, and one set of DNA instruction housed in one nucleus is often insufficient for the job. Therefore, these cells often have two or more nuclei in order to get the job done.  In these ways, specialization of organelle compartments and combinations allows for specialization of cellular function.

Centrioles are organelles important for the cellular
division. They are also a target for cancer therapy,
since many cancer cells have more than the regular
set of two centrioles.
As we have seen in every topic we have investigated, there are exceptions in the world of organelles. Some organelles are not membrane bound bags that carry things around or house certain reactions. Ribosomes are cellular organelles that make proteins, but they have no membrane. The cytoskeleton elements help the cell hold its structure, help the cell move, and help move other organelles move around within the cell, but they are not membrane bound either. Other cellular components, like the mitotic spindles of the centrioles that pull chromosomes apart when the cell undergoes mitosis are proteins that are present at only certain times in the animal cell. Even more confusing, plant cells divide similar to animal cells, but don’t have centriole organelles.

The take home message is that these organelles, whether membrane bound or not, perform vital services for the cell and make the many cellular reactions possible. The general modus operandi for organelles is that they carry out their functions with in the cell, but one type of organelle is the exception, it’s the traveling organelle.

Song RL, Liu XZ, Zhu JQ, Zhang JM, Gao Q, Zhao HY, Sheng AZ, Yuan Y, Gu JH, Zou H, Wang QC, & Liu ZP (2014). New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts. Genetics and molecular research : GMR, 13 (3), 4776-87 PMID: 25062413

Saltman LH, Javed A, Ribadeneyra J, Hussain S, Young DW, Osdoby P, Amcheslavsky A, van Wijnen AJ, Stein JL, Stein GS, Lian JB, & Bar-Shavit Z (2005). Organization of transcriptional regulatory machinery in osteoclast nuclei: compartmentalization of Runx1. Journal of cellular physiology, 204 (3), 871-80 PMID: 15828028


For more information on organelles, see:

Organelles –

Thursday, October 5, 2017

More Than The Sum Of Its Parts

Biology concepts – symbiosis, lichen products, weathering, pedogenesis

During the Depression, the Civilian Conservation
Corps got the idea to have unemployed people earn
some money by planting kudzu vine in the South to
reduce erosion. It seemed like a good idea at the
time, but in biology, not all good ideas stay good
ideas. Yes, there is a cabin under all that vine.
Will today’s good idea be tomorrow’s bust? In nature, an adaptation may provide an advantage today, yet be the cause of extinction tomorrow. Conditions rarely remain the same and never duplicate themselves. Very few organisms could develop identically at different times and places – but lichens are the exception.

Genetic studies of lichens from different places and of different ages show us that these amazing organisms have developed numerous times. This doesn’t mean that different lichens have appeared and gone extinct, only to make a comeback. It means that at least seven times in the history of life on Earth, a fungus and a photobiont (algae or cyanobacteria) have developed the exact same symbiotic relationship that we see in today's lichens.

Each of these original ideas has used different fungus types and sometimes different photobionts, but their relationship is identical in each case. Think of that, lichens are such a good idea that over 4 billion years, in deserts, forests, and coastlines lichens have invented themselves again and again. That must be one good idea!

One reason lichens have been so exceptional is that they can survive in places that can’t support much life. This may be the link in the separate development of lichens time and time again. One reason for their success in desolate environments is that they are veritable chemical factories. They make many products, some of which have uses in their stark homelands. Many of these products are unique to lichens.

Lichen acids (also called lichen substances or lichen products) are chemicals made by the lichen by further processing of regular cellular products, making them secondary metabolites. Lichens make 600-800 of these products, and all but 60-80 of them are unique to lichens.

The lichens themselves can be different colors, based on their
constituents. However, their colors may be hidden under the
different lichen products excreted from the cortex onto the thallus.
Here the lichen products are white and crystalline, and probably
mean that the conditions aren’t great for lichen growth.
Even more amazing, neither the fungus nor the algae (or cyanobacteria) that make up the lichen produce lichen acids when they are on their own. Many are made by the fungal component of the lichen, but the type of photobiont included in the symbiosis will control which lichen acids can be made. Most are produced as crystalline powders that are deposited extracellularly, on the stalks or the thallus bodies.

Making lichen acids would be wasted energy if they did not confer some advantage to the lichen, and evidence suggests that they do have specific functions. Lichens that are growing rapidly (for them, still might be only 1 mm/year) make very little of these lichen products. When exerting energy to make biomass, the lichen doesn’t need the lichen acids. This suggests that the acids are most needed when the going is tough, when lichens are trying to survive in poor conditions, ie. on difficult substrates, in drought, in extreme temperature or radiation, etc.

What is more, there must be very specific functions for the different acids based on what the lichen needs to do to survive. Lichens of identical morphology and made up of the same component fungus and algae can make very different acids, depending on their location or environment. Lichens can be grouped into complexes of similar organisms, but they may make different lichen acids.

For example, the Ramalina siliquosa complex of lichens is found on the Atlantic coastline of Europe. Low on the cliffs, most exposed to the sun and saltwater, R. cuspidate produces a lichen acid called stictic acid. However, high on the cliffs, away from the wind and facing toward the continent, R. crassa produces lots of hypoprotocetraric acids, but no stictic acid at all. Finally, R. stenoclada lives in the region between the other lichens, and produces a different lichen acid, norstictic acid. These different positions must present different growth challenges, and the lichens respond by making different acids.

So what do these lichen products do for the symbiots? They can dissolve rock to help anchor the lichen, and they can increase membrane permeability to permit flow of carbohydrates from the photobiont to the mycobiont. Many functions have been proposed and demonstrated, and one lichen acid, usnic acid, is a particularly good example of many of these functions.

Usnic acid is a dye that provides many advantages to the lichen,
but has also been a traditional dye for yarn for hundreds of years.
Usnic acid was first described in 1844, and is a yellow-green dye. Its color provides protection for the lichen from damage by visible and UV light, but this is just the beginning. Usnic acid is also important for protection of the lichen from predation. It has anti-herbivore properties, meaning that tastes bad or is toxic to the snails that like to make a meal of lichens. It has the same effect on insects and many fungi and microbes.

Antibacterial properties are particular strong for usnic acid. Many lichen acids are effective against a group of bacteria called Gram+. These include Mycobacterium tuberculae, several streptococci and staphylococci and some pnemuococcus. But a 2011 study indicates that usnic acid can go even further, and is toxic to Helicobacter pylori, the organism responsible for causing many stomach ulcers. Importantly, the usnic acid is not toxic to the photobiont component, whether it be cyanobacteria or algae. In addition, usnic acid has demonstrated anti-inflammatory properties and is a painkiller (analgesic).

But the most promising and surprising activity of lichen acids is as a degrader of prion proteins. Misfolded prion proteins are lethal to humans and other organisms (see -An Infectious Genetic Disease) and are resistant to being broken down by all known human protease enzymes. But a few lichens can produce a protease that destroys prions, some down to the level of undetectability.  Fungi themselves are susceptible to prion diseases, so this may be why the lichens produce anti-prion enzymes, but no one has checked lichens for prions. Not enough is known yet to predict if lichen products could be used as treatments for Creutzfeld-Jakob or fatal familial insomnia; here’s your chance to win a Nobel Prize!

This may be an important human use for lichens, but humans have been using lichens for thousands of years. Many of the dyes we use are lichen acid based, as is the litmus dye used in pH paper. Other uses have been more inventive, like as stuffing in Egyptian mummies and in Native American Indian diapers! If these don’t appeal to you, perhaps the Iceland-made lichen schnapps will be more your style. It supposedly tastes a lot like mouthwash.

However, we are amateurs compared to lichens in using the lichen acids. Lichens also use these products to grown on rocks. No soil needed. Crustose lichens are firmly attached to rock surfaces; they can’t be separated without damage…. to the rock.

Some lichens can protect themselves from poor environments by
Living within the rocks. Euendolithic lichens, like the one shown
above, bore into the rock using lichen acids, and then grow under
the surface of the rock. “You make a better door than a window,”
apparently doesn’t apply to rocks, because the endolithic lichens still
get enough light to perform photosynthesis.
Lichen acids can chemically weather rock by literally dissolving it. This provides crevices for the lichen to attach itself. Lichens can live on top of the rock (epilithic, epi = on top, and lith = stone), or they can be endolithic (within the stone). Within endolithic types, they can be chasmolithic, meaning they limit themselves to the fissures in the rocks and between the mineral grains, or they may be cryptoendolithic, meaning that the lichens grow within natural cavities in the rock. Finally, there is euendolithic lichens, and these are the toughest guys. They can dissolve the rock to the point of boring directly into the rock and creating its own cavities. Interestingly, the lichen will absorb much of the dissolved minerals, up to concentrations that would kill other organisms. This may prevent predation by making the lichen toxic to things that might eat it.

This ability to grow below the surface of a rock is exceptional. The photobiont must still be close enough to the surface to receive sunlight, but growing beneath the surface can protect the lichen from destructive forces of nature. Together with lichen acid protection from UV radiation and the lichens ability to survive extreme temperatures, the ability to grown inside rocks has implications for space travel. 

We know that lichens can survive in space (I’m Likin’ The Lichen) and growing inside rocks would protect them from re-entry temperatures, so could lichens have arrived on Earth from outer space? Pangenesis is the theory that life on Earth arriving from other planets, and lichens seem like a natural for this process. Unfortunately, pangenesis is most often considered with bacteria alone, and as a theory it has not got much to support it. But it is still an interesting proposition.

This rock is getting a good does of biological weathering. Tree roots,
lichens, and probably burrowing animals are all working to reduce
this noble boulder to gravel.
Growing inside rocks and dissolving the rock as needed promotes weathering breaking down of rock). Two type of weathering are brought about by lichen grown. Physical weathering comes primarily from turgor pressure. When the lichen takes up water (when it can get some), it swells and puts pressure on the fissures of the rock. Over time, this will lead to cracks and parts of the rock falling off.

There is also chemical weathering. This comes from the lichen acids dissolving the rock. Some of the minerals are mixed with the bits of rock that break off due to physical weathering and the organic material left over from dead lichens. All together, this makes soil. The process of pedogenesis (soil formation) is an important aspect of lichen growth. Making soil promotes the succession of bigger and more complex life forms, which then continue the weathering and soil formation. Look around you, all that dirt outside your window, deeper than you could dig, is there because of lichens started it all off – amazing. Lichens could be the most important player when it comes to human terraforming (terra = Earth and form = make like) another planet for future colonization.

Lichen growth on Easter Island. This ancient
statues can’t survive much Moai!
Not everything about weathering rock by lichens is good; consider their effects on stone statues. Some people say that the covering is protective, keeping the wind and sun from damaging the statue, but other say the chemical weathering promotes their breakdown. At Mount Rushmore, workers actively scrub the mountain to remove lichens and prevent the aging of Presidents Lincoln, Roosevelt, Jefferson, and Truman. How would you like to have that job, hanging off a cliff scrubbing out Theodore Roosevelt’s huge nostrils?

There is a strange dichotomy with lichens. They have arisen many times. They live thousands of years. They live in space, surviving radiation, extreme temperatures, and dryness. But lichens are very susceptible to pollution, it kills them or stops their growth.  Lichens have billions of years of success behind them, but it took humans to find a way to kill them off. As such, we now use lichens as indicator species, to determine if pollution concentrations are affecting nature. They built our world, now maybe they can help us to save it.

Heng Luo, Yoshikazu Yamamoto, Hae-Sook Jeon, Yan Peng Liu, Jae Sung Jung, Young Jin Koh and Jae-Seoun Hur (2011). Production of Anti-Helicobacter pylori metabolite by the lichen-Forming fungus Nephromopsis pallescens Journal of Microiology DOI: 10.1007/s12275-011-0289-9

For more information on lichen products, biological weathering, or pedogenesis, see:

Lichen acids –

Biological weathering –

Pedogenesis –