Why do mitochondria retain their own genome?

July 24, 2015 by Christopher Packham, Phys.org report
Mitochondria. Credit: Wikipedia commons

It sounds like science fiction to suggest that every cell in the human body is occupied by a tiny genome-equipped organelle, with which we exist in symbiosis. But in actuality, eukaryotic life is dependent on mitochondria, which provide energy to the cell in the form of adenosine triphosphate (ATP). Over millennia, the genomes of mitochondria evolved under selection for minimal gene content, but researchers have been unable to determine why some but not all mitochondrial genes have been transferred to the nuclear genome.

An international collaborative of researchers formed an interesting hypothesis regarding this phenomenon: The mitochondrial genome encodes hydrophobic membrane proteins which, if encoded in the nucleus, would be filtered by the signal recognition particle (SRP) and misdirected into the endoplasmic reticulum. The researchers conducted a study exploring their hypothesis and have published their results in the Proceedings of the National Academy of Sciences.

In order to predict if a would be targeted by SRP, the researchers calculated the free insertion energy of , which, if scored zero or less, were considered to be hydrophobic. Higher scores were rated marginally hydrophobic. If a transmembrane protein domain (TMD) scored hydrophobic and the length of its tail was longer than 120 , the researchers predicted it would be arrested by SRP and directed into the endoplasmic reticulum.

They expressed such proteins in cellular cytoplasm and were able to determine that they were, in fact, arrested by the SRP and directed to the endoplasmic reticulum. Further, the researchers observed that the mistargeting of these hydrophobic proteins into the soluble medium of the endoplasmic reticulum resulted in the formation of aberrant honeycomb structures similar to those observed during viral infections. "We conclude that genes for hydrophobic membrane proteins of more than 120 amino acids are likely retained in distinct organelle genomes to ensure a correct localization of these proteins and avoid transport to the endoplasmic reticulum," the authors write.

Thus, the researchers conclude, the selection against mistargeting hydrophobic proteins into the posed at least one major selective constraint on the retention of the . They bolster this finding by comparing it to similar membrane dynamics in the chloroplasts of plants.

Previous studies have suggested that one-third of have evolved in response to the specific environmental constraints of different species. Most of these proteins are involved with transport, regulatory, and membrane functions. The results of the current study are consistent with these findings.

A persistent mystery has been the evidence that in rare cases, transfers of otherwise universal into the have occurred. The results of the current study present an explanation: These particular proteins demonstrate reduced hydrophobicity in those species in which the transfer took place.

Clinical applications include the development of methods to cure human mitochondrial genetic diseases, such as Leber's hereditary optic neuropathy. "These results resolve the long-standing question about why aerobic mitochondria and photosynthetic chloroplasts need a distinct compartmental genome, by and large, although other factors may be involved," the authors write.

Explore further: Structural data reveals new mechanism behind protein transport

More information: "Mitochondrial genomes are retained by selective constraints on protein targeting." PNAS 2015 ; published ahead of print July 20, 2015, DOI: 10.1073/pnas.1421372112

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12 comments

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Whydening Gyre
5 / 5 (3) Jul 24, 2015
kinda like the Universe - always in motion...
docile
Jul 24, 2015
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docile
Jul 24, 2015
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Telekinetic
1.7 / 5 (6) Jul 24, 2015
My interest in mitochondria involves keeping my own in good working order. I supplement with MitoQ and Niagen (nicotinamide riboside). MitoQ is a form of CoenzymeQ10 that is roughly 800 times more potent than others, and Niagen is a precursor of NAD+ which is involved in the production of ATP. I expect I'll be conversing with your great grandchildren on this forum. I'll give them your regards.
RobertKarlStonjek
5 / 5 (2) Jul 25, 2015
Other theories conclude that those mitochondrial genes that have moved to the cell nucleus are synthesized for all the mitochondria in around the same abundances at the same time, whereas the genes that remain in mitochondria synthesize products needed for each particular mitochondria in an amount and at time to suit each individual mitochondrion's requirements.

It is likely, then, that both theories contribute to the overall solution of this mystery.
Torbjorn_Larsson_OM
4.8 / 5 (5) Jul 25, 2015
Other factors involved would be Lane's energy theory on mitochondria. Robert has already commented to this effect, but here is my more lengthy take:

Eukaryote energy density (protein turnover) is larger than in prokaryotes because endosymbiotically simplified mitochondria constitute local and cheap-to-produce-and-maintain energy producers.

Genes that are used by the mitochondria for respiration need massive expression and increase fitness if not expressed by the nucleus with its costly expression. Conversely genes that are not used by mitochondria for respiration need less expression and would increase fitness if expressed by the nucleus at its slower pace.

Since the SRP system seems to separate proteins by way of hydrophobicity, it seems rather a convenient way for evolution to sort out the proteins. The null hypothesis seems weak in this work, and perhaps they have got the mechanisms backwards.
Torbjorn_Larsson_OM
5 / 5 (4) Jul 25, 2015
@docile: I don't know about Warburg's beliefs, but the consensus is that the phylogenetic tree evidence that place mitochondria as rooted in alphaproteobacteria is overwhelming. [ https://en.wikipe...n#Origin ]

The last, best tree place mitochondria in a parasitic clade. It seems they were initially stealing ATP by an ancestral ATP importer membrane protein, but after being genetically bound to their hosts for survival they happened to coopt an ATP exporter instead. (Likely because they got infected by a retrovirus when their host was, and the virus carried - retroviral fashion - an ATP exporter that became stuck.)

@Telekinetic: This site is a science site and its material is based on evidence, not a trash dump for non-evidence personal anecdotes and especially about anti-science woo. Go to the woo sites with your personal quirks, they love that garbage. (And no, the longest lived are those that get an education instead. ;-)
Torbjorn_Larsson_OM
5 / 5 (4) Jul 25, 2015
[ctd] Also, I forgot, but it is important:

Research has now showed that people who abuse supplements without actually needing them live a shorter life. Makes sense, since they are bioactive compounds and having too much can be as harmful as producing or eating too little. It appears that even water soluble (urine eliminated) vitamins are harmful when ingested as pills. (E.g. getting too much vitamin C from fruits is not a problem, because we evolved to handle that.)

I can't point you to a specific papers, but the result appeared a few years back and should be googleable. Everybody should know this before they abuse their body, especially those who ironically and sadly do it voluntarily believing in the opposite effect.
docile
Jul 25, 2015
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Telekinetic
3 / 5 (2) Jul 25, 2015
@Torborn Larsson:

Dr. David Sinclair, a Harvard professor of genetics founded Niagen, makers of a nicotinamide riboside supplement, is by far a greater authority on longevity than you. Two-time Nobel laureate Linus Pauling recommended Vitamin C as a supplement because foods will not supply adequate amounts. Your DIS-information deprives people who read it an opportunity to repair their health or those they may know who are ill. Doctors routinely prescribe Vit. D3 as a supplement and prevents nine types of cancer. Close to 80% of the population is deficient in magnesium. The mythology that you subscribe to has cost many their lives.
JVK
2 / 5 (4) Jul 25, 2015
Re: "...both theories contribute to the overall solution of this mystery."

You seem to have missed the point of including biological facts that link thermodynamic cycles of protein biosynthesis and degradation to RNA-mediated gene duplication and RNA-mediated amino acid substitutions that differentiate the cell types of all individuals of all genera via their physiology of reproduction. http://youtu.be/DbH_Rj9U524

Others seem to have missed this blatant misrepresentation: "...eukaryotic life is dependent on mitochondria, which provide energy to the cell in the form of adenosine triphosphate (ATP).

Eukaryotic life is nutrient-energy dependent, which means it must be linked to the sun's biological energy by the de novo creation of amino acids and RNA-mediated events linked to gene duplication and cell type differentiation via the physiology of reproduction. Starting from the automagical creation of mitochondria is pseudosceintific nonsense.
weathervane
not rated yet Jul 25, 2015
So in summary if we transferred some of the genes from the mitochondria to the nucleus. Then we believe those gene products would just automatically end up labeled for transport to the endoplasic reticulum? Didn't the SENS institute already try this with human cells? So wonder what's happening under the bonnet in those altered cells?

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