This post has taken a long time to gestate. It’s aim is to turn the idea of the mitochondrion as a symbiotic guest within the cell, a ‘slave’ under nuclear control, into the proposition that the mitochondrion is much, much more than a vestigial organism and may be the most successful genome ever to appear on this planet.
There is a huge amount to unpack from the paragraph above so I will break it down into its component stories.
Symbiont and ‘Guest’
It was in the 1960s that Lynn Margulis first proposed the idea that the organelles which possessed their own DNA were the descendants of once free living organisms. Both are energy transducing organelles; the chloroplast using light energy to split hydrogen from water and use it to build carbohydrate by reducing carbon dioxide; the mitochondrion conversely oxidised organic compounds ( carbohydrates and fats) to produce chemical energy in the form of ATP.
The chloroplast and the mitochondrion have their own circular prokaryote-like DNA and the apparatus to transcribe and translate its code.Both are capable of replication, fusion and fission and both can senesce. In other words they look like many other bacteria-like organisms. Unfortunately it is obvious that in their DNA there is simply not enough genetic material to build a new organelle. Most of the genetic material for the building of these organelles is housed within the nucleus of the cell.
It is not a great step thereafter to propose that these organelles were once free living organisms that were ingested by chance into the host organism and have been taken over and fully integrated into the identity of their host organism. The host benefits from the ability of the organelles to generate free energy which is able to power the low entropy state that is a complex multicellular organism.
The host may have been itself once a large prokaryote- like phagocytic organism capable of metabolising the carbohydrates produced by ingested photosynthetic bacteria and so was bound to ingest the mitochondria which outside would have been oxidising hydrocarbon oily materials in their environment.
The paragraphs above briefly describe what is now, thanks to Margulis’ decades of argument, orthodoxy.
Why did mitochondria give up their DNA?
The answer is no one knows. It is easier to imagine ‘how’ since mitochondria and bacteria in general have circular plasmid DNA for which so called ‘horizontal transfer’, ie the passing of genetic material directly from one organism to another is the norm rather than the exception. But ‘why’ or even ‘when’ is a matter of speculation.
The answer may lie in the nature of the modern mitochondrion. It is capable of astonishing energy output in the form of ATP and Hydrogen ( in the form of reduced forms of NAD+ and FAD). It comes at a high price. Imagine a fast sports engine running at red-line revs 24/7 spitting out bullets in all directions. Mitochondria are like this in the sense that at full power oxidative-phosphorylation, as it is called, spits out immense numbers of damaging free radicals. The cell’s cytoplasm contains a lot of resources for catching and dealing with these radicals, using anti-oxidants and specialised enzymes, not to mention the repair of anything that got in the way of a stray bullet. So imagine the potential damage to an internal genome, especially a large, naked and complex genome. Free living bacteria could not operate at this level of energy output as their genomes would soon be wrecked.
Mitochondria found themselves inside a cell which was living on carbohydrates, probably produced by ingested photosynthetic organisms. The biochemistry of glycolysis to metabolise these carbohydrates means that the waste end products are acetyl units, or in other words simple pre-digested food for mitochondria.
. The end result would be potentially overfed, over stimulated mitochondria.
If the new guests were to be able to ramp up energy output as above , their DNA would have to be shielded. So why not put the important bits of its genome somewhere safe? Behind a double membrane and coated with protein would be ideal.
The nucleus as a store room.
One of ideas with many adherents about the mysterious origin of the nucleus is that it was once basically a lysosomal-like storage zone for intrusive viral and bacterial DNA/RNA. A bag of alien junk genes safely stored behind a double membrane wall. This model would suit the mitochondrion ‘outsourcing’ its genes to a place where they won’t get wrecked by its supercharged metabolism.
Conventionally, however this happened, the nucleus today controls the synthesis, repair and replication of mitochondria from a ‘central command’ model of the nucleus. However it is hard to imagine this being possible at the beginning. How would mitochondria reproduce and repair before the command and control nuclear model if their genes were locked away inside? Maybe gene transfer did not take place until the modern nucleus was up and running but if so how could mitochondrial DNA survive inside the high powered organelle? Possibly those chimeric cells that had increasing amounts of shielded mitochondrial DNA survived and vice versa.
One thing for sure, genes were transferred as mitochondria became hyper- energetic.
Retrograde signalling.
Recent developments have highlighted the fact that mitochondria and chloroplasts do not sit dumbly around awaiting orders from the nucleus. They have a complex signalling process that can ‘order up’ protein synthesis from the nuclear genes relevant to themselves and to the needs of the wider cellular environment. They act as sensors for the intracellular world,
But the use of the word ‘sensors’ implies a subservient role and I would rather like to think of them being ‘sensitive’ to their environment. The reasons for this are in the following paragraphs.
The presence of retrograde signaling mechanisms, as yet only barely elucidated, means that in the past mitochondria could, using such signalling systems, potentially ‘outsource’ their DNA and still make use of it … safely stored in the proto-nucleus.
Grim reapers.
We have long been used to the idea of mitochondria initiating cell death.This is known as apoptosis. It occurs when mitochondria are badly damaged or senesce. Senescence is normal for mitochondria in aged post-mitotic cells. Failing or unused cells are destroyed by a chain reaction initiated by mitochondria leaking a redox protein called Cytochrome C.
Mitochondria become leakier with age but will appear as a rejuvenated population if the cell undergoes mitosis, even in aged animals.
Mitochondria determine whether a cell lives or dies. But what about whether it reproduces?
Mitochondria and cell division.
Cell division requires a lot of energy. This is because there is a large decrease in the thermodynamic concept called entropy. Entropy can be driven in the negative direction with so-called Free Energy. Mitochondria provide 7.2 kj of Free Energy per molecule of ATP they produce.
It comes as no surprise that during cell division, scanning electron microscopy shows clearly that a large part of the population of mitochondria has fused to form a network of reticulate mitochondria seemingly bonded to the outer surface of the nucleus. The obvious inference is that a lot of energy is being supplied to drive the complex process of reproduction.
From a mitochondrial point of view, the reproduction of a cell presses a reset button for the mitochondrial population … and so is a good thing from their point of view.
A new perspective.
All of the above is pretty mainstream stuff and not the source of hot debate. What I would like to do is to change how we view mitochondria. To me they are not slaves to act merely as producers of free energy and to act as environmental sensors for the mission control centre which is the mighty nucleus. To me mitochondria are still free-living and reproducing their genetic material in a world that is the eukaryotic cytoplasm.
From a selfish-gene perspective mitochondria have distributed their genes throughout the entire biosphere of plants and animals. Cells without mitochondria are almost non-existent and certainly could not participate in the energy hungry multicellular world. And so the basic genetic building plan for mitochondria could be regarded as the most successful gene-machine of all time.
But there is the small matter of the bewildering diversity of the multicellular world Mitochondria could not be responsible for this? No, not directly, but indirectly they certainly could. If in some imagined past there were mitochondria living in a host and they had outsourced their genes to the bag of DNA described earlier. Inevitably when powering-up their own cell division there would be unintended recipients within the store of DNA postulated as the proto-nucleus. Bizarre and unpredictable results of countless explosive forms would emerge to be nurtured or eliminated by natural selection. Eventually things would settle down and the pre-cambrian explosion 540 million years ago would fade into history.
There we have it, the ultimate mito-centric world. Not so much a useful passenger symbiont handily providing energy in an oxygen rich world, more a fundamental driver of multicelluar life as a result of it own genes’ ‘desire’ to survive
Mitochondrial DNA is no longer ‘stand-alone’ DNA. Xenobiotic transfer of mitochondria is possible between closely related species but it falls away with ‘genetic distance’. For example all of the mitochondrial DNA recovered from late Neanderthals is actually Homo Sapiens mtDNA, gorilla mtDNA will work in Chimp but embryos do not develop and so on.
This story is a classic ‘chicken and egg’ story for today the nucleus and mitochondria are intimately integrated.
How that journey proceeded is unknown. But one thing's for sure, mitochondria were centre stage and still are:
Here is a potential timeline::
4 billion years ago = the start of life?
3.7 billion years ago. First photosynthetic life Energy capture and transduction on the surface begins
2.7 billion years ago archea develop actin proteins and phagocytosis starts. Heterotrophic life begins
2.3 billion years ago Cyanobacteria’s oxygen changes atmosphere, oils and carbohydrates accumulate
2.3 billion years ago free living proto-mitochondria oxidising hydrocarbons
600 million years ago chimeric cell starts to ‘power-up’ mitochondria use endogenous acetyl groups and outsource genes to proto-nucleus Massive increase in transduction of energy originating from light
540 million years ago Cambrian explosion of extraordinary multicellular diversity.
440 million years ago the first mass extinction.
