title: The antiapoptotic OPA1/Parl couple participates in mitochondrial adaptation to heat shock.
abstract: The mitochondria-shaping protein optic atrophy 1 (OPA1) has genetically distinguishable roles in mitochondrial morphology and apoptosis. The latter depends on the presenilin associated rhomboid like (PARL) protease, essential for the accumulation of a soluble intermembrane space form of OPA1 (IMS-OPA1). Here we show that OPA1 and PARL participate in the heat shock response, a stereotypical cellular process of adaptation to thermal stress. Upon heat shock, long forms of OPA1 are lost and mitochondria fragment. However, mitochondrial fusion is dispensable to maintain viability, whereas IMS-OPA1 is required. Upon conditioning-a process of mild heat shock and recovery-IMS-OPA1 accumulates, OPA1 oligomers increase and mitochondria release less cytochrome c, ultimately resulting in cellular resistance to subsequent apoptotic inducers. In Parl(-/-) cells accumulation of IMS-OPA1 is blunted and conditioning fails to protect from cytochrome c release and apoptosis. Thus, the OPA1/PARL dependent pathway of cristae remodeling is implicated in heat shock. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).
authors.affiliation: Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Luiza K
authors.initials: LK
authors.lastname: Sanjuán Szklarz
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*
chemical_list: D024101:Mitochondrial Proteins; D045304:Cytochromes c; D045726:Metalloproteases; C512710:PARL protein, mouse; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse