Tondera, Daniel and Grandemange, Stephanie and Jourdain, Alexis and Karbowski, Mariusz and Mattenberger, Yves and Herzig, Sebastien and Da Cruz, Sandrine and Clerc, Pascaline and Raschke, Ines and Merkwirth, Carsten and Ehses, Sarah and Krause, Frank and Chan, David C. and Alexander, Christiane and Bauer, Christoph and Youle, Richard and Langer, Thomas and Martinou, Jean-Claude (2009) SLP-2 is required for stress-induced mitochondrial hyperfusion. Embo Journal, 28 (11). pp. 1589-1600. ISSN 0261-4189 http://resolver.caltech.edu/CaltechAUTHORS:20090903-083208055
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Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress.
|Additional Information:||© 2009 European Molecular Biology Organization. Received: 24 November 2008; accepted: 12 March 2009; published online: 9 April 2009. We thank Dr Mihara and Dr Ishihara for rat OPA1-V1, OPA1-V1DS1, OPA1-V7, and AIF-OPA1-V7230–997 cDNAs, Dr Scorrano for OPA1 cDNA, Dr Rojo for human Mfn1 cDNA, Professor Wiesner for 143B rho0 cells, Professor Picard for pdtTomato-C1, Dr Dencher and Dr Madrenas for support, Dr Rossignol for his advices and all members of the lab for fruitful discussions. This work was funded by the Deutsche Forschungsgemeinschaft (DFG) (TO540/1-1), the NIH intramural program, the Swiss National Science Foundation (subsidy 3100A0-109419/1), Oncosuisse Trust, Roche Research Foundation and the Geneva Department of Education. FK is funded in part by the European Union (MiMage, EC FP6 Contract No. LSHM-CT-2004-512020).|
|Subject Keywords:||ATP; fusion; mitochondria; stress; survival|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||22 Sep 2009 16:40|
|Last Modified:||26 Dec 2012 11:18|
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