The incredible shrinking organelle

Considering its central role in energy metabolism in almost all eukaryotes, the mitochondrion is an amazingly plastic organelle, both evolutionarily and functionally. The few genes that the mitochondrial genome (mitochondrial DNA; mtDNA) encodes are clearly bacterial in origin—emanating from the α-proteobacterial lineage—supporting the widely held view that the mitochondrion is the evolutionary remnant of a bacterial symbiont (Gray et al, 2001). However, contemporary mitochondria are nothing like contemporary bacteria. For one thing, even the most gene-rich mtDNA encodes far less genetic information than the most gene-poor bacterial genome, and mitochondrial genomes are different from bacterial genomes in form, organization and mode of expression; these features vary tremendously among diverse eukaryotes. Mitochondrial genomes might be circular, linear or even highly fragmented, and they might contain highly fragmented and rearranged genes. Only within a poorly studied group of eukaryotic microbes—protists—known as jakobid flagellates does the mtDNA resemble a typical, albeit highly reduced, bacterial genome.

In addition, the mitochondrial proteome is not only overwhelmingly (>90%) encoded in the nucleus, but only a small proportion (10–15%) is demonstrably α-proteobacterial in evolutionary affiliation. Thus, in the evolutionary transition from bacterial symbiont to integrated organelle, the mitochondrion has undergone an impressive degree of re-tailoring, shedding the bulk of its genetic information and taking on proteins of diverse evolutionary origins. Moreover, this re-tailoring is highly variable within different eukaryotic lineages, with an intriguing chunk of the mitochondrial proteome seeming to be organism-specific—lacking demonstrable sequence homologues other than in very close evolutionary relatives.

Although the evolutionary shrinkage of the mitochondrial genome is well-documented, what is less widely appreciated is the wholesale shrinkage of the organelle itself in certain anaerobic eukaryotes. Taken to its extreme, such shrinkage involves complete loss of the mitochondrial genome, with a consequent reduction in the structural complexity and biochemical versatility of the organelle. This simplification might include elimination of the electron-transport chain (ETC) and thus lead to inability of the resulting mitochondrion-related organelle (MRO) to carry out a key function of aerobic mitochondria: ATP synthesis through coupled oxidative phosphorylation (for a full account, see Hjort et al, 2010).

One such MRO, the hydrogenosome, is a hydrogen-producing organelle that was originally characterized in an anaerobic protist, Trichomonas vaginalis. The T. vaginalis hydrogenosome lacks mtDNA as well as components of the classic mitochondrial ETC, relying instead on substrate-level phosphorylation to generate ATP. Initially, the resemblance between the anaerobic biochemistry of the T. vaginalis MRO and that of anaerobic bacteria such as Clostridia raised the possibility that the hydrogenosome might have a different evolutionary origin than the classic aerobic mitochondrion. However, studies of hydrogenosomal proteins have demonstrated that the hydrogenosome is an evolutionarily derived (remnant) mitochondrion. Hydrogenosomes have been found in eukaryotes that are widely separated in phylogenetic trees, and in such trees, anaerobic, hydrogenosome-containing eukaryotes are often interspersed with close relatives that grow aerobically and contain conventional mitochondria. This punctate phylogenetic distribution suggests that the transition from mitochondrion to hydrogenosome has happened repeatedly and independently throughout eukaryotic evolution.

The mitosome, an even more shrunken MRO that has not only dispensed entirely with a genome, but also has no ATP-generating capacity. This MRO was discovered in anaerobic eukaryotes that were initially thought to lack mitochondria entirely, the postulate being that they diverged away from the main line of eukaryotic evolution prior to the symbiosis that led to the mitochondrion. However, in all supposedly amitochondriate protists that have been examined, a candidate mitosome has been identified. As with hydrogenosomes, a punctate phylogenetic distribution of mitosomes is emerging.

Recently, intermediate forms of 'shrinking organelle' have been identified in the anaerobic protists Nyctotherus ovalis, Blastocystis sp. and Proteromonas lacertae (Hjort et al, 2010; Pérez-Brocal et al, 2010; de Graaf et al, 2011), relatives of brown algae and diatoms. In these cases, regions of the mtDNA that code for terminal portions of the ETC and for the mitochondrial ATP synthase have been discarded. The remaining DNA specifies genes for components of a mitochondrial translation system, as well as subunits of a proton-pumping complex I (NADH:ubiquinone oxidoreductase); a remarkable example—comparing the ciliate Nyctotherus with the stramenopiles Blastocystsis or Proteromonas—of convergent mtDNA evolution. These observations suggest that the transitional MROs of Nyctotherus, Blastocystis and Proteromonas retain a partial ETC, as well as the ability to synthesize protein, whereas other data (EST surveys) indicate that they are metabolically more complex than either hydrogenosomes or mitosomes. The discovery of these particular MROs is important because their existence argues that the transition from fully fledged aerobic mitochondrion to fully fledged anaerobic mitosome proceeds through, and might stop at, several intermediate stages: a realization that not only dramatically emphasizes the evolutionary and functional versatility of the mitochondrion, but also opens the possibility that we might yet uncover still other variations of this incredible shrinking organelle.