Table 4.

Lethal and vital functions of evolutionarily distant cell death effectors

Protein	Species	Role in apoptosis	Role in normal metabolism
AIF	Saccharomyces cerevisiae	IM-associated FAD-containing protein facing the IMS Translocates from mitochondria to nuclei to form an active nuclease with CypA Participates in chronological aging	AIF KO induces a defect in the respiratory chain (mainly complex III)
CED-4	Caenorhabditis elegans	Ortholog of mammalian Apaf-1 Cytosolic allosteric activator of the caspase CED-3	Participates in DNA-damage induced cell cycle arrest of germ cells downstream of ATM and ATL
CED-9	Caenorhabditis elegans	Ortholog of mammalian Bcl-2/Bcl-XL Sequester CED-4, thereby inhibiting the activation of CED-3 caspase	Involved with EGL-1 in the regulation of mitochondrial fusion/fission dynamics
EGL-1	Caenorhabditis elegans	BH3-only protein Interacts with CED-9 (a Bcl-2 ortholog) to competitively displace CED-4	Required for optimal induction of autophagy in response to starvation Involved with CED-9 in the regulation of mitochondrial fusion/fission dynamics
EndoG	Saccharomyces cerevisiae	IMS protein Translocates from mitochondria to nuclei to mediate chromatinolysis Participates in chronological aging	Required for the survival of tetraploid cells

Abbreviations: AIF, apoptosis-inducing factor; Apaf-1, apoptotic protease activating factor 1; BH, Bcl-2 homology domain; CypA, cyclophilin A; EndoG, endonuclease G; FAD, flavine adenine nucleotide; IM, mitochondrial inner membrane; IMS, mitochondrial intermembrane space; KO, knockout.