Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Summary: Major insights into the phylogenetic distribution, biochemistry, and evolutionary significance of organelles involved in ATP synthesis (energy metabolism) in eukaryotes that thrive in anaerobic environments for all or part of their life cycles have accrued in recent years. All known eukaryotic groups possess an organelle of mitochondrial origin, mapping the origin of mitochondria to the eukaryotic common ancestor, and genome sequence data are rapidly accumulating for eukaryotes that possess anaerobic mitochondria, hydrogenosomes, or mitosomes. Here we review the available biochemical data on the enzymes and pathways that eukaryotes use in anaerobic energy metabolism and summarize the metabolic end products that they generate in their anaerobic habitats, focusing on the biochemical roles that their mitochondria play in anaerobic ATP synthesis. We present metabolic maps of compartmentalized energy metabolism for 16 well-studied species. There are currently no enzymes of core anaerobic energy metabolism that are specific to any of the six eukaryotic supergroup lineages; genes present in one supergroup are also found in at least one other supergroup. The gene distribution across lineages thus reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style. Some facultative anaerobes have retained both aerobic and anaerobic pathways. Diversified eukaryotic lineages have retained the same enzymes of anaerobic ATP synthesis, in line with geochemical data indicating low environmental oxygen levels while eukaryotes arose and diversified.     

Hydrogenosomes: eukaryotic adaptations to anaerobic environments.

Like mitochondria, hydrogenosomes compartmentalize crucial steps of eukaryotic energy metabolism; however, this compartmentalization differs substantially between mitochondriate aerobes and hydrogenosome-containing anaerobes. Because hydrogenosomes have arisen independently in different lineages of eukaryotic microorganisms, comparative analysis of the various types of hydrogenosomes can provide insights into the functional and evolutionary aspects of compartmentalized energy metabolism in unicellular eukaryotes.     

An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle.

The evolutionary processes underlying the differentness of prokaryotic and eukaryotic cells and the origin of the latter's organelles are still poorly understood. For about 100 years, the principle of endosymbiosis has figured into thoughts as to how these processes might have occurred. A number of models that have been discussed in the literature and that are designed to explain this difference are summarized. The evolutionary histories of the enzymes of anaerobic energy metabolism (oxygen-independent ATP synthesis) in the three basic types of heterotrophic eukaryotes those that lack organelles of ATP synthesis, those that possess mitochondria and those that possess hydrogenosomes--play an important role in this issue. Traditional endosymbiotic models generally do not address the origin of the heterotrophic lifestyle and anaerobic energy metabolism in eukaryotes. Rather they take it as a given, a direct inheritance from the host that acquired mitochondria. Traditional models are contrasted to an alternative endosymbiotic model (the hydrogen hypothesis), which addresses the origin of heterotrophy and the origin of compartmentalized energy metabolism in eukaryotes.     

Hydrogenosomes, mitochondria and early eukaryotic evolution

Available data suggest that unusual organelles called hydrogenosomes, that make ATP and hydrogen, and which are found in diverse anaerobic eukaryotes, were once mitochondria. The evolutionary origins of the enzymes used to make hydrogen, pyruvate:ferredoxin oxidoreductase (PFO) and hydrogenase, are unresolved, but it seems likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobes, these proteins are found in diverse eukaryotic cells, including our own, where they are targeted to different cell compartments. Organelles related to mitochondria and hydrogenosomes have now been found in species of anaerobic and parasitic protozoa that were previously thought to have separated from other eukaryotes before the mitochondrial endosymbiosis. Thus it is possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, bearing testimony to the important role that the mitochondrial endosymbiosis has played in eukaryotic evolution. It remains to be seen if members of this family of organelles share a common function essential to the eukaryotic cell, that provides the underlying selection pressure for organelle retention under different living conditions.     

Single eubacterial origin of eukaryotic sulfide:quinone oxidoreductase,a mitochondrial enzyme conserved from the early evolution of eukaryotes during anoxic and sulfidic times

Mitochondria occur as aerobic, facultatively anaerobic, and, in the case of hydrogenosomes, strictly anaerobic forms. This physiological diversity of mitochondrial oxygen requirement is paralleled by that of free-living alpha-proteobacteria, the group of eubacteria from which mitochondria arose, many of which are facultative anaerobes. Although ATP synthesis in mitochondria usually involves the oxidation of reduced carbon compounds, many alpha-proteobacteria and some mitochondria are known to use sulfide (H2S) as an electron donor for the respiratory chain and its associated ATP synthesis. In many eubacteria, the oxidation of sulfide involves the enzyme sulfide:quinone oxidoreductase (SQR). Nuclear-encoded homologs of SQR are found in several eukaryotic genomes. Here we show that eukaryotic SQR genes characterized to date can be traced to a single acquisition from a eubacterial donor in the common ancestor of animals and fungi. Yet, SQR is not a well-conserved protein, and our analyses suggest that the SQR gene has furthermore undergone some lateral transfer among prokaryotes during evolution, leaving the precise eubacterial lineage from which eukaryotes obtained their SQR difficult to discern with phylogenetic methods. Newer geochemical data and microfossil evidence indicate that major phases of early eukaryotic diversification occurred during a period of the Earth's history from 1 to 2 billion years before present in which the subsurface ocean waters contained almost no oxygen but contained high concentrations of sulfide, suggesting that the ability to deal with sulfide was essential for prokaryotes and eukaryotes during that time. Notwithstanding poor resolution in deep SQR phylogeny and lack of a specifically alpha-protebacterial branch for the eukaryotic enzyme on the basis of current lineage sampling, a single eubacterial origin of eukaryotic SQR and the evident need of ancient eukaryotes to deal with sulfide, a process today germane to mitochondrial quinone reduction, are compatible with the view that eukaryotic SQR was an acquisition from the mitochondrial endosymbiont.     

A single eubacterial origin of eukaryotic pyruvate: ferredoxin oxidoreductase genes: implications for the evolution of anaerobic eukaryotes.

The iron sulfur protein pyruvate: ferredoxin oxidoreductase (PFO) is central to energy metabolism in amitochondriate eukaryotes, including those with hydrogenosomes. Thus, revealing the evolutionary history of PFO is critical to understanding the origin(s) of eukaryote anaerobic energy metabolism. We determined a complete PFO sequence for Spironucleus barkhanus, a large fragment of a PFO sequence from Clostridium pasteurianum, and a fragment of a new PFO from Giardia lamblia. Phylogenetic analyses of eubacterial and eukaryotic PFO genes suggest a complex history for PFO, including possible gene duplications and horizontal transfers among eubacteria. Our analyses favor a common origin for eukaryotic cytosolic and hydrogenosomal PFOs from a single eubacterial source, rather than from separate horizontal transfers as previously suggested. However, with the present sampling of genes and species, we were unable to infer a specific eubacterial sister group for eukaryotic PFO. Thus, we find no direct support for the published hypothesis that the donor of eukaryote PFO was the common alpha-proteobacterial ancestor of mitochondria and hydrogenosomes. We also report that several fungi and protists encode proteins with PFO domains that are likely monophyletic with PFOs from anaerobic protists. In Saccharomyces cerevisiae, PFO domains combine with fragments of other redox proteins to form fusion proteins which participate in methionine biosynthesis. Our results are consistent with the view that PFO, an enzyme previously considered to be specific to energy metabolism in amitochondriate protists, was present in the common ancestor of contemporary eukaryotes and was retained, wholly or in part, during the evolution of oxygen-dependent and mitochondrion-bearing lineages.     

On Bacterial Origin of Mitochondria in Eukaryotes in the Light of Current Ideas of Evolution of the Organic World

The hypothesis of bacterial origin of mitochondria, which existed until the end of the 20th century, has been confirmed on the basis of the current concepts of organic world evolution in the open sea hydrosphere and original data on the entry of bacteria (prokaryotes) in the cells of eukaryotes and their transformation into the mitochondrial mechanism of aerobic energy metabolism. This hypothesis can now be considered as a factually substantiated theory. The process of endocytosis of bacteria in the tissues of eukaryotes, which began at the onset of transition of the anaerobic state of open sea hydrosphere and land atmosphere (Early Proterozoic), is considered as the beginning of symbiotic mode of life of organisms of the Proterozoic and Postproterozoic organic world.     

A New Aspect to the Origin and Evolution of Eukaryotes

One of the most important omissions in recent evolutionary theory concerns how eukaryotes could emerge and evolve. According to the currently accepted views, the first eukaryotic cell possessed a nucleus, an endomembrane system, and a cytoskeleton but had an inefficient prokaryotic-like metabolism. In contrast, one of the most ancient eukaryotes, the metamonada Giardia lamblia, was found to have formerly possessed mitochondria. In sharp contrast with the traditional views, this paper suggests, based on the energetic aspect of genome organization, that the emergence of eukaryotes was promoted by the establishment of an efficient energy-converting organelle, such as the mitochondrion. Mitochondria were acquired by the endosymbiosis of ancient α-purple photosynthetic Gram-negative eubacteria that reorganized the prokaryotic metabolism of the archaebacterial-like ancestral host cells. The presence of an ATP pool in the cytoplasm provided by this cell organelle allowed a major increase in genome size. This evolutionary change, the remarkable increase both in genome size and complexity, explains the origin of the eukaryotic cell itself. The loss of cell wall and the appearance of multicellularity can also be explained by the acquisition of mitochondria. All bacteria use chemiosmotic mechanisms to harness energy; therefore the periplasm bounded by the cell wall is an essential part of prokaryotic cells. Following the establishment of mitochondria, the original plasma membrane-bound metabolism of prokaryotes, as well as the funcion of the periplasm providing a compartment for the formation of different ion gradients, has been transferred into the inner mitochondrial membrane and intermembrane space. After the loss of the essential function of periplasm, the bacterial cell wall could also be lost, which enabled the naked cells to establish direct connections among themselves. The relatively late emergence of mitochondria may be the reason why multicellularity evolved so slowly. Received: 29 May 1997 / Accepted: 9 October 1997     

The rise of oxygen and complex life

Mitochondria have been put forward as the saviours of anaerobes when their environment became oxygenated. However, despite oxygenic photosynthesis evolving around 2.7 billion years ago (Ga), followed by the "Great Oxidation" of the atmosphere ~ 2.4 Ga, the deep oceans remained largely anoxic and either iron-enriched or sulphidic until 580 million years ago, when the eukaryotic radiation was well underway. Atmospheric oxygen probably remained at an intermediate concentration (1-10% of the present level) from ~ 2.4 until ~ 0.8 Ga when a "lesser oxidation" began. This drastically changes the textbook view of the ecological conditions under which the mitochondrial endosymbiont established itself. It could explain the widespread distribution of anaerobic biochemistry in every eukaryotic supergroup: anaerobic biochemistry is hard-wired into the eukaryotes.     

Analysis of two genomes from the mitochondrion-like organelle of the intestinal parasite Blastocystis: complete sequences, gene content, and genome organization

Acquisition of mitochondria by the ancestor of all living eukaryotes represented a crucial milestone in the evolution of the eukaryotic cell. Nevertheless, a number of anaerobic unicellular eukaryotes have secondarily discarded certain mitochondrial features, leading to modified organelles such as hydrogenosomes and mitosomes via degenerative evolution. These mitochondrion-derived organelles have lost many of the typical characteristics of aerobic mitochondria, including certain metabolic pathways, morphological traits, and, in most cases, the organellar genome. So far, the evolutionary pathway leading from aerobic mitochondria to anaerobic degenerate organelles has remained unclear due to the lack of examples representing intermediate stages. The human parasitic stramenopile Blastocystis is a rare example of an anaerobic eukaryote with organelles that have retained some mitochondrial characteristics, including a genome, whereas they lack others, such as cytochromes. Here we report the sequence and comparative analysis of the organellar genome from two different Blastocystis isolates as well as a comparison to other genomes from stramenopile mitochondria. Analysis of the characteristics displayed by the unique Blastocystis organelle genome gives us an insight into the initial evolutionary steps that may have led from mitochondria to hydrogenosomes and mitosomes.     

Early cell evolution,eukaryotes, anoxia,sulfide, oxygen,fungi first (?), and a tree of genomes revisited

Genomes contain evidence for the history of life and furthermore contain evidence for lateral gene transfer, which was an important part of that history. The geological record also contains evidence for the history of life, and newer findings indicates that the Earth's oceans were largely anoxic and highly sulfidic up until about 0.6 billion years ago. Eukaryotes, which fossil data indicate to have been in existence for at least 1.5 billion years, must have therefore spent much of their evolutionary history in oxygen-poor and sulfide-rich environments. Many eukaryotes still inhabit such environments today. Among eukaryotes, organelles also contain evidence for the history of life and have preserved abundant traces of their anaerobic past in the form of energy metabolic pathways. New views of eukaryote phylogeny suggest that fungi may be among the earliest-branching eukaryotes. From the standpoint of the fungal feeding habit (osmotrophy rather than phagotrophy) and from the standpoint of the diversity in their ATP-producing pathways, a eukaryotic tree with fungi first would make sense. Because of lateral gene transfer and endosymbiosis, branches in the tree of genomes intermingle and occasionally fuse, but the overall contours of cell history nonetheless seem sketchable and roughly correlateable with geological time.     

Multiple secondary origins of the anaerobic lifestyle in eukaryotes

Classical ideas for early eukaryotic evolution often posited a period of anaerobic evolution producing a nucleated phagocytic cell to engulf the mitochondrial endosymbiont, whose presence allowed the host to colonize emerging aerobic environments. This idea was given credence by the existence of contemporary anaerobic eukaryotes that were thought to primitively lack mitochondria, thus providing examples of the type of host cell needed. However, the groups key to this hypothesis have now been shown to contain previously overlooked mitochondrial homologues called hydrogenosomes or mitosomes; organelles that share common ancestry with mitochondria but which do not carry out aerobic respiration. Mapping these data on the unfolding eukaryotic tree reveals that secondary adaptation to anaerobic habitats is a reoccurring theme among eukaryotes. The apparent ubiquity of mitochondrial homologues bears testament to the importance of the mitochondrial endosymbiosis, perhaps as a founding event, in eukaryotic evolution. Comparative study of different mitochondrial homologues is needed to determine their fundamental importance for contemporary eukaryotic cells.     

The origin of eukaryotes: the difference between prokaryotic and eukaryotic cells.

Eukaryotes have long been thought to have arisen by evolving a nucleus, endomembrane, and cytoskeleton. In contrast, it was recently proposed that the first complex cells, which were actually proto-eukaryotes, arose simultaneously with the acquisition of mitochondria. This so-called symbiotic association hypothesis states that eukaryotes emerged when some ancient anaerobic archaebacteria (hosts) engulfed respiring alpha-proteobacteria (symbionts), which evolved into the first energy-producing organelles. Therefore, the intracellular compartmentalization of the energy-converting metabolism that was bound originally to the plasma membrane appears to be the key innovation towards eukaryotic genome and cellular organization. The novel energy metabolism made it possible for the nucleotide synthetic apparatus of cells to be no longer limited by subsaturation with substrates and catalytic components. As a consequence, a considerable increase has occurred in the size and complexity of eukaryotic genomes, providing the genetic basis for most of the further evolutionary changes in cellular complexity. On the other hand, the active uptake of exogenous DNA, which is general in bacteria, was no longer essential in the genome organization of eukaryotes. The mitochondrion-driven scenario for the first eukaryotes explains the chimera-like composition of eukaryotic genomes as well as the metabolic and cellular organization of eukaryotes.     

The terrestrial biota prior to the origin of land plants (embryophytes): a review of the evidence

It is often assumed that life originated and diversified in the oceans prior to colonizing the land. However, environmental constraints in chemical evolution models point towards critical steps leading to the origin of life as having occurred in subaerial settings. The earliest fossil record does not include finds from terrestrial deposits, so much of our understanding about the presence of a terrestrial microbial cover prior to the Proterozoic is based on inference and geochemical proxies that indicate biospheric carbon cycling during the Archaean. Our assessment is that by 2.7 Ga, microbial ecosystems in terrestrial settings were driven by oxygen‐generating, photosynthetic cyanobacteria. Studies of modern organisms indicate that both the origin and primary diversification of the eukaryotes could have occurred in terrestrial settings, shortly after 2.0 Ga, but there is no direct fossil evidence of terrestrial eukaryotes until about 1.1 Ga. At this time, it appears that the diversity of life in non‐marine habitats exceeded that found in marine settings where sulphidic seas may have impaired eukaryotic physiology and retarded evolution. Geochemical proxies indicate the establishment of an extensive soil‐forming microbial cover by 850 Ma, and it is possible that a rise in atmospheric oxygen at this time was due to the evolutionary expansion of green algae into terrestrial habitats. Direct fossil evidence of the earliest terrestrial biotas in the Phanerozoic consists of problematical palynomorphs from the Cambro‐Ordovician of Laurentia. These indicate that the evolution of the first land plants (embryophytes) during the Middle Ordovician took place within a landscape that included aeroterrestrial algae which were actively adapting to selection in subaerial settings.     

Bifunctional aldehyde/alcohol dehydrogenase (ADHE) in chlorophyte algal mitochondria

Protein profiles of mitochondria isolated from the heterotrophic chlorophyte Polytomella sp. grown on ethanol at pH 6.0 and pH 3.7 were analyzed by Blue Native and denaturing polyacrylamide gel electrophoresis. Steady-state levels of oxidative phosphorylation complexes were influenced by external pH. Levels of an abundant, soluble, mitochondrial protein of 85 kDa and its corresponding mRNA increased at pH 6.0 relative to pH 3.7. N-terminal and internal sequencing of the 85 kDa mitochondrial protein together with the corresponding cDNA identified it as a bifunctional aldehyde/alcohol dehydrogenase (ADHE) with strong similarity to homologues from eubacteria and amitochondriate protists. A mitochondrial targeting sequence of 27 amino acids precedes the N-terminus of the mature mitochondrial protein. A gene encoding an ADHE homologue was also identified in the genome of Chlamydomonas reinhardtii, a photosynthetic relative of Polytomella. ADHE reveals a complex picture of sequence similarity among homologues. The lack of ADHE from archaebacteria indicates a eubacterial origin for the eukaryotic enzyme. Among eukaryotes, ADHE has hitherto been characteristic of anaerobes since it is essential to cytosolic energy metabolism of amitochondriate protists such as Giardia intestinalis and Entamoeba histolytica. Its abundance and expression pattern suggest an important role for ADHE in mitochondrial metabolism of Polytomella under the conditions studied. The current data are compatible with the view that Polytomella ADHE could be involved either in ethanol production or assimilation, or both, depending upon environmental conditions. Presence of ADHE in an oxygen-respiring algal mitochondrion and co-expression at ambient oxygen levels with respiratory chain components is unexpected with respect to the view that eukaryotes acquired ADHE genes specifically as an adaptation to an anaerobic lifestyle.     

Mitochondria and hydrogenosomes are two forms of the same fundamental organelle

Published data suggest that hydrogenosomes, organelles found in diverse anaerobic eukaryotes that make energy and hydrogen, were once mitochondria. As hydrogenosomes generally lack a genome, the conversion is probably one way. The sources of the key hydrogenosomal enzymes, pyruvate : ferredoxin oxidoreductase (PFO) and hydrogenase, are not resolved by current phylogenetic analyses, but it is likely that both were present at an early stage of eukaryotic evolution. Once thought to be restricted to a few unusual anaerobic eukaryotes, the proteins are intimately integrated into the fabric of diverse eukaryotic cells, where they are targeted to different cell compartments, and not just hydrogenosomes. There is no evidence supporting the view that PFO and hydrogenase originated from the mitochondrial endosymbiont, as posited by the hydrogen hypothesis for eukaryogenesis. Other organelles derived from mitochondria have now been described in anaerobic and parasitic microbial eukaryotes, including species that were once thought to have diverged before the mitochondrial symbiosis. It thus seems possible that all eukaryotes may eventually be shown to contain an organelle of mitochondrial ancestry, to which different types of biochemistry can be targeted. It remains to be seen if, despite their obvious differences, this family of organelles shares a common function of importance for the eukaryotic cell, other than energy production, that might provide the underlying selection pressure for organelle retention.     

Anaerobic animals from an ancient,anoxic ecological niche

Tiny marine animals that complete their life cycle in the total absence of light and oxygen are reported by Roberto Danovaro and colleagues in this issue of BMC Biology. These fascinating animals are new members of the phylum Loricifera and possess mitochondria that in electron micrographs look very much like hydrogenosomes, the H₂-producing mitochondria found among several unicellular eukaryotic lineages. The discovery of metazoan life in a permanently anoxic and sulphidic environment provides a glimpse of what a good part of Earth's past ecology might have been like in 'Canfield oceans', before the rise of deep marine oxygen levels and the appearance of the first large animals in the fossil record roughly 550-600 million years ago. The findings underscore the evolutionary significance of anaerobic deep sea environments and the anaerobic lifestyle among mitochondrion-bearing cells. They also testify that a fuller understanding of eukaryotic and metazoan evolution will come from the study of modern anoxic and hypoxic habitats.     

Mitochondrial type iron-sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS

Pyridoxal-5'-phosphate-dependent cysteine desulfurase (IscS) is an essential enzyme in the assembly of FeS clusters in bacteria as well as in the mitochondria of eukaryotes. Although FeS proteins are particularly important for the energy metabolism of amitochondrial anaerobic eukaryotes, there is no information about FeS cluster formation in these organisms. We identified and sequenced two IscS homologs of Trichomonas vaginalis (TviscS-1 and TviscS-2) and one of Giardia intestinalis (GiiscS). TviscS-1, TviscS-2, and GiiscS possess the typical conserved regions implicated in cysteine desulfurase activity. N-termini of TviscS-1 and TviscS-2 possess eight amino acid extensions, which resemble the N-terminal presequences that target proteins to hydrogenosomes in trichomonads. No presequence was evident in GiiscS from Giardia, an organism that apparently lacks hydrogenosmes or mitochondria. Phylogenetic analysis showed a close relationship among all eukaryotic IscS genes including those of amitochondriates. IscS of proteobacteria formed a sister group to the eukaryotic clade, suggesting that isc-related genes were present in the proteobacterial endosymbiotic ancestor of mitochondria and hydrogenosomes. NifS genes of nitrogen-fixing bacteria, which are IscS homologs required for specific formation of FeS clusters in nitrogenase, formed a more distant group. The phylogeny indicates the presence of a common mechanism for FeS cluster formation in mitochondriates as well as in amitochondriate eukaryotes. Furthermore, the analyses support a common origin of Trichomonas hydrogenosomes and mitochondria, as well as secondary loss of mitochondrion/hydrogenosome-like organelles in Giardia.     

Paleobiological Perspectives on Early Eukaryotic Evolution

Eukaryotic organisms radiated in Proterozoic oceans with oxygenated surface waters, but, commonly, anoxia at depth. Exceptionally preserved fossils of red algae favor crown group emergence more than 1200 million years ago, but older (up to 1600–1800 million years) microfossils could record stem group eukaryotes. Major eukaryotic diversification ∼800 million years ago is documented by the increase in the taxonomic richness of complex, organic-walled microfossils, including simple coenocytic and multicellular forms, as well as widespread tests comparable to those of extant testate amoebae and simple foraminiferans and diverse scales comparable to organic and siliceous scales formed today by protists in several clades. Mid-Neoproterozoic establishment or expansion of eukaryophagy provides a possible mechanism for accelerating eukaryotic diversification long after the origin of the domain. Protists continued to diversify along with animals in the more pervasively oxygenated oceans of the Phanerozoic Eon.Eukaryotic organisms have a long evolutionary history, recorded, in part, by conventional and molecular fossils. For the Phanerozoic Eon (the past 542 million years), eukaryotic evolution is richly documented by the skeletons (and, occasionally, nonskeletal remains) of animals, as well as the leaves, stems, roots, and reproductive organs of land plants. Phylogenetic logic, however, tells us that eukaryotes must have a deeper history, one that began long before the first plant and animal fossils formed. To what extent does the geological record preserve aspects of deep eukaryotic history, and can the chemistry of ancient sedimentary rocks elucidate the environmental conditions under which the eukaryotic cell took shape?     

Hydrogenosomes: convergent adaptations of mitochondria to anaerobic environments

Hydrogenosomes are membrane-bound organelles that compartmentalise the final steps of energy metabolism in a number of anaerobic eukaryotes. They produce hydrogen and ATP. Here we will review the data, which are relevant for the questions: how did the hydrogenosomes originate, and what was their ancestor? Notably, there is strong evidence that hydrogenosomes evolved several times as adaptations to anaerobic environments. Most likely, hydrogenosomes and mitochondria share a common ancestor, but an unequivocal proof for this hypothesis is difficult because hydrogenosomes lack an organelle genome - with one remarkable exception (Nyctotherus ovalis). In particular, the diversity of extant hydrogenosomes hampers a straightforward analysis of their origins. Nevertheless, it is conceivable to postulate that the common ancestor of mitochondria and hydrogenosomes was a facultative anaerobic organelle that participated in the early radiation of unicellular eukaryotes. Consequently, it is reasonable to assume that both, hydrogenosomes and mitochondria are evolutionary adaptations to anaerobic or aerobic environments, respectively.