Proteins that fuse and fragment mitochondria in apoptosis: con-fissing a deadly con-fusion?
During apoptosis, mitochondria undergo multiple changes that culminate in the release of cytochrome c and other proapoptotic cofactors. Recently, a role for previously overlooked morphological changes, fission of the mitochondrial reticulum and remodeling of mitochondrial cristae, has been suggested in mammalian cells and in developmental apoptosis of C. elegans. Mitochondrial morphology is determined by fusion and fission processes, controlled by a growing set of "mitochondria-shaping" proteins, whose levels and function appear to regulate the mitochondrial pathways of cell death. Expression of pro-fusion proteins, as well as of inhibition of pro-fission molecules reduces apoptosis, suggesting a linear relationship between fragmentation and death. Mechanisms by which mitochondrial fragmentation promotes apoptosis and interactions between fragmentation and remodeling of the inner membrane are largely unclear. A tempting, unifying hypothesis suggests that fission is coupled to cristae remodeling to maximize cytochrome c release.
Scorrano
Luca
L
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, I-35129 Padua, Italy. luca.scorrano@unipd.it
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000502:physiology; D004718:Saccharomycetales / Q000502:physiology
D024101:Mitochondrial Proteins; D045304:Cytochromes c