SLP‐2 is required for stress‐induced mitochondrial hyperfusion |
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| Authors: | Alexis Jourdain Mariusz Karbowski Yves Mattenberger Sébastien Herzig Pascaline Clerc Ines Raschke Carsten Merkwirth Sarah Ehses Frank Krause David C Chan Christiane Alexander Christoph Bauer Richard Youle Thomas Langer Jean‐Claude Martinou |
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| Affiliation: | 1. Department of Cell Biology, University of Geneva, Geneva, Switzerland;2. Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD, USA;3. Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA;4. Institute for Genetics and Centre for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany;5. Physical Biochemistry, Department of Chemistry, Technische Universit?t Darmstadt, Darmstadt, Germany;6. Division of Biology, California Institute of Technology, Pasadena, CA, USA;7. Department of Neuroscience, Max‐Delbrück‐Center for Molecular Medicine, Berlin, Germany;8. Imaging Platform, NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland |
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| Abstract: | 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. |
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| Keywords: | ATP fusion mitochondria stress survival |
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