Thread by @sam_soete

Mitochondria: An Epic Origin Story

What are they? Where do they come from? And why are they here?

This 🧵unravels the mystery behind the origins of the most important and enigmatic organelle in our body.

#mitochondria #metabolism #science #biology

In the depths of time, when the universe was but a tender babe, an epoch unfathomable, there existed naught but primordial cells.

1.5 billion years ago, a singular ancient invasion by a eubacteria of an archea host occurred.

This invasion or engulfing, depending on who or what we give the moral high-ground, may have been the quintessential step in the most important evolutionary leap since the origin of life itself:

The transition from a primitive cell to a complex higher organism (eukaryote).

Behold, the primal emergence of the mighty mitochondria, heralding a revolution in the ancient tapestry of life itself.

Witness the birth of the powerhouse that would forever change the course of evolution, setting the stage for extraordinary complexity and boundless energy.

Despite relentless inquiry, the enigmatic origins of this extraordinary entity continue to elude our grasp, leaving behind a trail of unanswered questions that reverberate through the corridors of scientific exploration.

Did mitochondria arise at the same time as the rest of the eukaryotic cell?

Did it originate under anaerobic or aerobic conditions?

What is the evolutionary relationship between mitochondria and hydrogenosomes?

This thread will explore all of them in detail. Let's dig in.

First lets take a look at the different types of organelles that appear to be derived from the same mitochondrial ancestry.

There are 4.

1) Aerobic Mitochondria: These respire oxygen during pyruvate breakdown and ATP synthesis, generating water and carbon dioxide as end products. These are present in the realm of mammals and plants.

2) Anaerobic Mitochondria: The extraordinary adaptation of invertebrates like worms and molluscs have mitochondria that defy convention by thriving in anaerobic environments, where oxygen is not their primary terminal electron acceptor.

3) Hydrogenosomes: These unique organelles, found in protists like trichomonads, ditch the ETC and opt for fermenting pyruvate, generating hydrogen as a by-product. Surprisingly, the enzymes within hydrogenosomes can also be found in other eukaryotes' mitochondria.

4. Mitosomes: Astonishingly, mitosomes forego ATP synthesis entirely, presenting a captivating puzzle in the study of cellular energy.

One interesting question is whether or not all mitochondria originate from a single ancestor.

The primal titan of cellular power.

The first mitochondrion.

Like eukaryotes themselves, mitochondria appear to have arisen from one pivotal origin.

Genome sequencing provides evidence for this perspective.

Firstly, in any particular mitochondrial genome (with few exceptions), genes that have an assigned function are a subset of those found in R. americana mtDNA.

Why is this relevant?

The most ancient, gene-rich mitochondrial genome to date is the 69,034 base pair (bp) mtDNA of R. americana.

Additionally, all known lineages of eukaryotes that possess hydrogenosomes or mitosomes branch as sisters to mitochondrion-bearing lineages.

Furthermore, a conserved set of clearly homologous and commonly inherited genes are preserved in the mtDNA across all known eukaryotic groups.

An example:

Aspects and components of the mitochondrial protein import process are conserved in hydrogenosomes and mitosomes, arguing strongly for common ancestry with mitochondria.

Having explored the origins of mitochondria and their shared ancestry, let us now delve into the captivating tale of how this intricate symbiotic bond between eubacteria and archaeal hosts came to be.

There are currently two main, competing theories about the origin of mitochondria.

The hypotheses proposed for this unique symbiosis both have metabolic underpinnings.

1) Oxygen Detoxification Hypothesis

This is the traditional hypothesis and assumes that the symbiotic relationship driven an aerobic proteobacterium relieving an anaerobic host from oxygen tension.

The initial benefit of the symbiosis might have been the endosymbiont's ability to detoxify oxygen for the anaerobe host.

This theory is supported by the fact that a steep rise in oxygen occurred 2.2 Ga.

But, evidence indicates that both archaea and proteobacteria coexisted 2.7 Ga, so they may have merged before the oxygen spike - thus supporting the anaerobic-driven hypothesis.

Furthermore, the oxygen detoxification process rests on shaky ground because the forms of oxygen that are toxic to anaerobes are ROS.

In eukaryotes, ROS are produced in mitochondria because of the oxygen involved in the mitochondrial ETC.

In that sense, mitochondria do not solve the ROS problem but create it.

This traditional view also does not account for anaerobic mitochondria or hydrogenosomes.

2) Hydrogen Hypothesis:

Alternatively, the hydrogen hypothesis suggests a methanogenic archaean host (producer of methane) that engulfed a methanotrophic proteobacterium (utilizer of methane) with the aim of obtaining compounds such as hydrogen.

This view assumes that ancestral mitochondria were metabolically flexible entities capable of living with or without oxygen (facultative anaerobes).

The hydrogen hypothesis rationalizes the aerobic and anaerobic capacities of organelles of mitochondrial ancestry such as hydrogenosomes.

The initial benefit of the symbiosis could have been the production of hydrogen by the endosymbiont as a source of energy and electrons for the archaebacterial host, which is thought to have been hydrogen dependent.

Because it posits that eukaryotes evolved from the mitochondrial endosymbiosis in a prokaryotic host, this theory directly accounts for the ubiquity of mitochondria among all eukaryotic lineages.

Ultimately, it is not clear what evolutionary bottleneck forged the unbroken alliance between the endosymbiont and its host.

We have no covered:

• The mystery of a single ancestral origin

• The potential mechanisms under which endosymbiosis took place

Next lets explore an irregularity present in the mitochondrial genome.

Eukaryotes are genetic chimeras.

Their genome consists of genes inherited vertically from their archae-bacterially related host as well as from the endosymbiont (mitochondria).

These include mitochondrially encoded genes for mitochondrial ribosomes.

Typical mitochondria are composed of over a thousand proteins.

But modern mitochondrial genomes only range from 3 to 67 protein-coding genes.

This paradox introduces our next topic: Genome Reduction

Gene sequencing has shown that mitochondria have undergone a streamlining process called reductive evolution, leading to a marked loss of coding capacity compared to that of their closest eubacterial relatives.

Many endosymbiont genes are lost forever, and many that remain have been transferred to the host's nucleus.

Mitochondrial DNA regularly escapes from the organelle and becomes integrated as copies into nuclear DNA.

Differential gene content in mtDNAs is attributable primarily to mitochondrion-to-nucleus gene transfer.

mtDNA may also lose genes whose functions are substituted for by unrelated genes encoded in the nucleus.

Genome reduction was key in transforming the autonomous endosymbiont into an organelle used for supplying its host with compartmentalized bioenergetic and biosynthetic factories.

As Nick Lane put it:

"They retain a fragment of a genome as a badge of former independence. Their tortuous relations with their host cells have shaped the whole fabric of life, from energy, sex, and fertility, to cell suicide, ageing, and death."

From ancient invasions to symbiotic bonds, the origin story of mitochondria unfolds.

They shaped complex organisms, defied convention, and sparked a revolution in the tapestry of life. Genome mysteries, metabolic hypotheses, and genome reduction unveil their remarkable journey.

That brings use to the end of this thread.

I am but a humble student of these cellular powerhouses, but if you want to learn more about mitochondria, check out @DrJackKruse's work.

He offers insights into how mitochondria relate to the rest of our body that nobody else does.

@DrJackKruse If you enjoyed this intellectual odyssey :

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#mitochondria #metabolism #biology #science