HIV-1 protease inhibitors and cytomegalovirus vMIA induce mitochondrial fragmentation without triggering apoptosis

Recent studies suggest that mitochondrial dynamics (fission and fusion) has a major impact on the regulation of mitochondrial outer membrane permeabilization, which in turn determines the point-of-no-return of apoptotic and necrotic cell death. Thus, programmed cell death, as it occurs in Caenorhabditis elegans development, is accompanied by mitochondrial fragmentation. Overexpression of a dominant-negative (DN) mutant of dynamin-related protein-1 (DRP-1), which inhibits mitochondrial fission, can reduce the incidence of cell death induced by a BH3-only protein in vivo, in C. elegans. These data confirm prior observations obtained in vitro, in mammalian cell culture systems, in which a DN point mutant of human DRP-1 (DRP-1K38A) was found to inhibit mitochondrial fragmentation and cell death induced by different apoptosis inducers. Conversely, the overexpression of wild-type DRP-1, which causes extensive mitochondrial fragmentation without cell death, can inhibit apop...