A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis.
Mitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release is accompanied by fragmentation of the mitochondrial reticulum and by remodelling of the internal structure of the organelle. Here we review data supporting the existence of a regulatory network in the inner mitochondrial membrane that includes optic atrophy 1 (Opa1), a dynamin-related protein, and presenilin-associated rhomboid-like (Parl), a rhomboid protease. Opa1 regulates remodelling of the cristae independent of its effect on fusion. Cristae remodelling conversely requires Parl, which participates in the production of a soluble form of Opa1 retrieved together with the integral membrane one in oligomers that are disrupted early during apoptosis. Parl itself is regulated by proteolysis to generate a cleaved form, which in turn modulates the shape of the mitochondrial reticulum. Cleavage of Parl depends on its phosphorylation state around the cleavage site, implicating mitochondrial kinases and phosphatases in the regulation of mitochondrial shape.
Pellegrini
L
L
Centre de Recherche Universite' Laval Robert Giffard, 2601 Ch. de la Canardiere, Quebec, Canada. Luca.Pellegrini@crulrg.vlaval.ca
Scorrano
L
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D019143:Evolution, Molecular; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation
D024101:Mitochondrial Proteins; D045726:Metalloproteases; D010447:Peptide Hydrolases; C485223:PARL protein, human; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human