The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane 
space, where it facilitates fusion between mitochondria. Apoptosis causes Opa1 
release into the cytosol and causes mitochondria to fragment. Loss of 
mitochondrial membrane potential also causes mitochondrial fragmentation but not 
Opa1 release into the cytosol. Both conditions induce the proteolytic cleavage 
of Opa1, suggesting that mitochondrial fragmentation is triggered by Opa1 
inactivation. The opposite effect was observed with knockdown of the 
mitochondrial intermembrane space protease Yme1. Knockdown of Yme1 prevents the 
constitutive cleavage of a subset of Opa1 splice variants but does not affect 
carbonyl cyanide m-chlorophenyl hydrazone or apoptosis-induced cleavage. 
Knockdown of Yme1 also increases mitochondrial connectivity, but this effect is 
independent of Opa1 because it also occurs in Opa1 knockdown cells. We conclude 
that Yme1 constitutively regulates a subset of Opa1 isoforms and an unknown 
mitochondrial morphology protein, whereas the loss of membrane potential induces 
the further proteolysis of Opa1.