Bax (Bcl2-associated X protein) is an apoptosis-inducing protein that 
participates in cell death during normal development and in various diseases. 
Bax resides in an inactive state in the cytosol of many cells. In response to 
death stimuli, Bax protein undergoes conformational changes that expose 
membrane-targeting domains, resulting in its translocation to mitochondrial 
membranes, where Bax inserts and causes release of cytochrome c and other 
apoptogenic proteins. It is unknown what controls conversion of Bax from the 
inactive to active conformation. Here we show that Bax interacts with humanin 
(HN), an anti-apoptotic peptide of 24 amino acids encoded in mammalian genomes. 
HN prevents the translocation of Bax from cytosol to mitochondria. Conversely, 
reducing HN expression by small interfering RNAs sensitizes cells to Bax and 
increases Bax translocation to membranes. HN peptides also block Bax association 
with isolated mitochondria, and suppress cytochrome c release in vitro. Notably, 
the mitochondrial genome contains an identical open reading frame, and the 
mitochondrial version of HN can also bind and suppress Bax. We speculate 
therefore that HN arose from mitochondria and transferred to the nuclear genome, 
providing a mechanism for protecting these organelles from Bax.