Friday, January 29, 2016

The mitochondrion: where did the powerhouse of the cell come from?

By Scott Miller

Nestled along the Minnesota River within view of the freeway, Black Dog Generating Station is an Xcel Energy power plant with a capacity of around 500 megawatts in Burnsville, Minnesota. Built in the 1950s, Black Dog generates power from coal and gas.1 As a child, I remember driving by this behemoth, seeing black curls of pollution rising into the sky. To me, it had always been a fixture along the river, but one day I questioned how this powerhouse got there. Biologists have had the same question about mitochondria.

Living organisms are broadly grouped into two camps: prokaryotes and eukaryotes. Prokaryotes encompass bacteria and another group of microbes called archaea, while eukaryotes include many microbes but also more complex organisms such as plants, fungi, and animals. Eukaryotes and prokaryotes differ in many ways, but eukaryotes generally have a membrane-bound nucleus, whereas prokaryotes do not.2 In addition to a nucleus, eukaryotic cells can have other membrane-bound organelles as well, though precisely which organelles the cells have depends on the species. Besides the nucleus, another common organelle is the mitochondrion. If there is one thing students remember from high school biology, it is that “mitochondria are the powerhouses of the cell.” This is (broadly) true, but most high school biology classes stop short of following up with a much more exciting lesson: where did mitochondria come from?

Biologists view life through an evolutionary lens. Novelties do not spontaneously arise; they have to come from something. Eukaryotes did not just suddenly sprout functioning mitochondria. Consequently, evolutionary biologists have developed a widely accepted theory for how these cells acquired their “powerhouses,” termed the endosymbiotic theory.3 According to the endosymbiotic theory, at some point in distant evolutionary history, one larger cell engulfed a smaller cell. The smaller cell continued to live inside the larger cell and perform functions similar to today’s mitochondria. Over generations and with evolution, the smaller cell lost its autonomy, evolving into the mitochondrion for the larger cell.

Mitochondria in bovine lymphocytes. 
The features of mitochondria support endosymbiotic theory in that they share many characteristics with prokaryotes, the likely “smaller cell.”4 First, mitochondria are roughly rod-shaped, reminiscent of the structure and size of many prokaryotes. The second feature is replication. In humans, for example, most cells replicate in a process called mitosis. Mitochondria, however, divide independently of mitosis in a process similar to binary fission, which is how bacteria replicate.5 Another feature of mitochondria supporting endosymbiotic theory is the presence of DNA inside mitochondria. Mitochondrial DNA is separate from the DNA found in a eukaryote’s nucleus and has a circular structure similar to DNA found in prokaryotes.

Biologists wanted to see if any existing species of eukaryotes and prokaryotes resembled an early mitochondrion and its larger host cell. Using modern sequencing techniques, biologists have been able to determine the combination and order of nucleotide bases that make up the DNA in mitochondria. Biologists have also been able to sequence the DNA from many prokaryotes. They can then compare the DNA from mitochondria and the DNA from prokaryotes. The idea is that similar DNA sequences correspond to a mitochondrion and prokaryotic species that are more closely related to each other.

Researchers consider the small freshwater eukaryote Reclimonas americana to have the most ancestral mitochondria; that is, the mitochondria in R. americana are the most similar to bacteria of any eukaryote. R. americana is part of a larger group of species called jakobids. Not all eukaryotes have mitochondria—though all eukaryotes have at least one nucleus—and jakobids are very similar to retortamonads, a different group of eukaryotes lacking mitochondria. A group of scientists from Canada and New England therefore hypothesized that jakobids represent a point in evolutionary history where eukaryotes first acquired mitochondria.6

 To test their hypothesis, these scientists examined the sequence of the DNA from R. americana’s mitochondria. The researchers found 92 functional genes in R. americana mitochondrial DNA, compared to only 37 in DNA from human mitochondria. The 92 genes included the code for several proteins normally found in bacteria. Of the 67 proteins that R. americana mitochondria can make with their DNA, 18 are not found in other eukaryotes’ mitochondria. Most notably, the researchers identified four rpo genes in R. americana, all of which had never been found in mitochondria prior to this study. The rpo genes contain the code for proteins called RNA polymerases, which play a prominent role in the biological process of transcription. The rpo genes found in R. americana’s mitochondria are usually only found in bacteria.

The researchers also identified other key features linking R. americana mitochondria to bacteria. One was organization of the DNA in the mitochondria. Bacterial DNA often contains operons, which are clusters of genes that have products with a similar function. For example, all of the genes coding for proteins involved in digesting lactose reside in the lac operon. The mitochondrial DNA in R. americana contains vestiges of operons. For example, the rpo genes were all linked together in the mitochondrial DNA. This organization provides further proof of a relatively close relation between R. americana mitochondria and bacterial cells.

Additionally, the researchers found evidence for Shine-Dalgarno-type sequences in R. americana mitochondrial DNA. Without elaborating on the technical details, Shine-Dalgarno sequences are normally a distinct characteristic of prokaryotes. If they are present in R. americana mitochondria, this constitutes additional evidence that these mitochondria are relatively closely related to prokaryotes.

In addition to finding which mitochondria are most related to prokaryotes, biologists have studied which prokaryotes are most similar to mitochondria. A group of French scientists compared the mitochondrial DNA sequence from R. americana to those of several bacterial species from the grouping known as the Rickettsiales order.7 Scientists have suspected that the bacterial ancestor of mitochondria came from the Rickettsiales. The French scientists analyzed the DNA sequence of nine genes found in both the bacteria and R. americana mitochondria. Using statistics and software, the researchers confirmed that the bacterial ancestor of mitochondria was related to other Rickettsiales. In particular, they determined that the bacterial species Pelagibacter ubique is most similar to R. americana mitochondria.

Research studies continue to support endosymbiotic theory for the origin of mitochondria. The current thought is that Reclimonas americana mitochondria are the most closely related to bacteria of any mitochondria. In turn, the bacterial species Pelagibacter ubique most closely resembles the bacteria that developed into mitochondria. While the picture is not entirely clear, biologists now have a much better idea of where mitochondria came from.

Works Cited
  1. Black Dog Generating Station, 2015. Available from: . [10 December 2015].
  2. John, P., and Bell, L. (2001). Viral Eukaryogenesis: Was the Ancestor of the Nucleus a Complex DNA Virus? Journal of Molecular Evolution 53(3), 251-256.
  3. Davidow, Y., Huchon, D., Koval, S.F., and Jurkevitch, E. (2006). A new α-proteobacterial clade of Bdellovribrio-like predators: implications for the mitochondrial endosymbiotic theory. Environmental Microbiology 8(12), 2179-2188.
  4. Gray, M.W., Burger, G., and Lang, B.F. (2001). The origin and early evolution of mitochondria. Genome Biol 2, reviews1018.1–reviews1018.5.
  5. Seo, A.Y., Joseph, A.-M., Dutta, D., Hwang, J.C.Y., Aris, J.P., and Leeuwenburgh, C. (2010). New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123, 2533–2542.
  6. Lang, B.F., Burger, G., O’Kelly, C.J., Cedergren, R., Golding, G.B., Lemieux, C., Sankoff, D., Turmel, M., and Gray, M.W. (1997). An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387, 493–497.
  7. Georgiades, K., Madoui, M.-A., Le, P., Robert, C., and Raoult, D. (2011). Phylogenomic Analysis of Odyssella thessalonicensis Fortifies the Common Origin of Rickettsiales, Pelagibacter ubique and Reclimonas americana Mitochondrion. PLoS ONE 6, e24857.

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