Origin and evolution of eukaryotic apoptosis: the bacterial connection
Cell Death and Differentiation
The availability of numerous complete genome sequences of prokaryotes and several eukaryotic genome sequences provides for new insights into the origin of unique functional systemsoftheeukaryotes.Severalkeyenzymesoftheapoptotic machinery, including the paracaspase and metacaspase families of the caspase-like protease superfamily, apoptotic ATPasesand NACHT familyNTPases, and mitochondrial HtrAlike proteases, have diverse homologs in bacteria, but not in
... alysisstronglysuggestsamitochondrial origin for metacaspases and the HtrA-like proteases, whereasacquisitionfromActinomycetesappearstobethemost likely scenario for AP-ATPases. The homologs of apoptotic proteins are particularly abundant and diverse in bacteria that undergo complex development, such as Actinomycetes, Cyanobacteria and a-proteobacteria, the latter being progenitorsofthemitochondria.Inthesebacteria,theapoptosis-related domainstypicallyformmultidomainproteins,whichareknown orinferredtoparticipateinsignaltransductionandregulationof geneexpression.Someofthesebacterialmultidomainproteins contain fusions between apoptosis-related domains, such as AP-ATPase fused with a metacaspase or a TIR domain. Thus, bacterial homologsof eukaryoticapoptoticmachinery componentsmightfunctionallyandphysicallyinteractwitheachother aspartsofsignalingpathwaysthatremaintobeinvestigated.An emerging scenario of the origin of the eukaryotic apoptotic system involves acquisition of several central apoptotic effectors as a consequence of mitochondrial endosymbiosis and probably also as a result of subsequent, additional horizontal gene transfer events, which was followed by recruitmentofnewlyemergingeukaryoticdomainsasadaptors.