Hydrogenosomes were isolated, purified, biochemically characterized and named in the early 1970s by D. G. Lindmark and M. Müller at Rockefeller University. In addition to this seminal study on hydrogenosomes, they also demonstrated, for the first time, the presence of pyruvate:ferredoxin oxido-reductase and hydrogenase in eukaryotes. Further studies were subsequently conducted on the biochemical cytology and subcellular organization of anaerobic protozoan parasites (Trichomonas vaginalis, Tritrichomonas foetus, Monocercomonas sp., Giardia lamblia, Entamoeba sp., and Hexamita inflata). Using information obtained from hydrogenosomal and biochemical cytology studies these researchers determined the mode of action of metronidazole (Flagyl) in 1976. Metronidazole is today recognized as the gold standard chemotherapeutic agent for the treatment of anaerobic infections caused by prokaryotes (Clostridium, Bacteroides, Helicobacter) and eukaryotes (Trichomonas, Tritrichomonas, Giardia, Entamoeba). Metronidazole is taken up by diffusion. Once taken up by anaerobes, it is non-enzymatically reduced by reduced ferredoxin which is produced by the action of pyruvate:ferredoxin oxido-reductase. This reduction creates products toxic to the anaerobic cell, and allows for selective accumulation of the drug in anaerobes.
Hydrogenosomes are approximately 1 micrometre in diameter but under stress conditions can reach up to 2 micrometre  and are so called because they produce molecular hydrogen. Like mitochondria, they are bound by distinct double membranes and one has an inner membrane with some cristae-like projections. Hydrogenosomes have evolved from mitochondria by loss of aerobiosis-related features in several lineages (not all hydrogenosomes are directly related). In most cases, hydrogenosomes are genomeless, though genomes have persisted in some lineages such as Neocallimastix, Trichomonas vaginalis or Tritrichomonas foetus. However, a hydrogenosomal genome has been detected in the cockroach ciliate Nyctotherus ovalis, and the stramenopile Blastocystis. The similarity between Nyctotherus and Blastocystis, which are only distantly related, is believed to be the result of convergent evolution, and calls into question whether there is a clear-cut distinction between mitochondria, hydrogenosomes, and mitosomes (another kind of degenerate mitochondria).
The anaerobic ciliated protozoan Nyctotherus ovalis, found in the hindgut of several species of cockroach, has numerous hydrogenosomes that are intimately associated with endosymbiotic methane-producing archaea, the latter using the hydrogen produced by the hydrogenosomes. The matrix of N. ovalis hydrogenosomes contains ribosome-like particles of the same size as a numerous type of ribosome (70s) of the endosymbiotic methanogenic archaea. This suggested the presence of an organellar genome which was indeed discovered by Akhmanova and later partly sequenced by Boxma.
Three multicellular species of Loricifera — Spinoloricus nov. sp., Rugiloricus nov. sp. and Pliciloricus nov. sp. — have been found deep in Mediterranean sediments, and use hydrogenosomes in their anaerobic metabolism cycle.
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