Determinants of cytochrome c pro-apoptotic activity: The role of lysine 72 trimethylation

Abstract

Cytochrome c released from vertebrate mitochondria engages apoptosis by triggering caspase activation. We previously reported that, whereas cytochromes c from higher eukaryotes can activate caspases in Xenopus egg and mammalian cytosols, iso-1 and iso-2 cytochromes c from the yeast Saccharomyces cerevisiae cannot. Here we examine whether the inactivity of the yeast isoforms is related to a post-translational modification of lysine 72, N-ε-trimethylation. This modification was found to abrogate pro- apoptotic activity of metazoan cytochrome c expressed in yeast. However, iso- 1 cytochrome c lacking the trimethylation modification also was devoid of pro-apoptotic activity. Thus, both lysine 72..