Although release of cytochrome c in yeast apoptosis has previously been reported, it is not known how it occurs.
Herein we used yeast genetics to investigate whether depletion of proteins putatively involved in MOMP and cytochrome c release affects these processes in yeast.
While deletion of POR1 (yeast voltage-dependent anion channel) enhances apoptosis triggered by acetic acid, H(2)O(2) and diamide, CPR3 (mitochondrial cyclophilin) deletion had no effect.
Absence of ADP/ATP carrier (AAC) proteins, yeast orthologues of ANT, protects cells exposed to acetic acid and diamide but not to H(2)O(2). Expression of a mutated form of Aac2p (op1) exhibiting very low ADP/ATP translocase activity indicates that AAC's pro-death role does not require translocase activity.
Absence of AAC proteins impairs MOMP and release of cytochrome c, which, together with other mitochondrial inner membrane proteins, is degraded.
Our findings point to a crucial role of AAC in yeast apoptosis.