The antiapoptotic OPA1/Parl couple participates in mitochondrial adaptation to heat shock

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• 作者：Luiza K. Sanju¨¢n Szklarz ; Luca Scorrano
• 关键词：BAK ; Bcl-2 associated killer ; BAX ; Bcl-2 associated protein X ; BCL-2 ; B-cell lymphoma 2 ; DRP1 ; dynamin related protein 1 ; FCCP ; cyanide m-fluorophenylhydrazone ; FIS1 ; fission 1 ; HSP ; heat shock protein ; IMM ; inner mitochondrial membrane ; IMS ; intermembran
• 刊名：Biochimica et Biophysica Acta (BBA)/Bioenergetics
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：1817
• 期：10
• 页码：1886-1893
• 全文大小：901 K

文摘

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¡ªa process of mild heat shock and recovery¡ªIMS-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).