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Elucidation of interactors of the pro-fusion proteins MFN1 and MFN2 sheds light on novel pathways regulating mitochondrial morphology in apoptosis

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Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4585 - 2013/08/08
Abstract Large-scale proteomics analysis provide information on the proteomic signatures including interacting partners and post-translational modification. In the first part of the thesis, we identified a novel keratin-binding protein, Trichoplein (TpMs) that requires MFN2 to modulate mitochondrial shape and tethering. In the second part, we show that the pleiotropic mitogen activated protein (MAP) kinase phosphorylate the pro-fusion protein mitofusin (MFN) 1, switching its functions in apoptosis and mitochondrial fusion. A phosphoproteomic analysis revealed that MFN1 is phosphorylated at an atypical ERK1 site (T562) of its HR1 domain. This site proved essential to mediate the MFN1-dependent mitochondrial elongation and regulation of apoptosis by the MEK/ERK pathway. A T562 mutant mimicking constitutive phosphorylation of MFN1 triggered mitochondrial fragmentation, increased susceptibility to apoptosis, bound more avidly to the proapoptotic BCL-2 family member BAK and facilitated its activation. Our data identify a role for phosphorylation of MFN1 in mitochondrial shape and apoptosis.
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URN: urn:nbn:ch:unige-294470
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PYAKUREL, Aswin. Elucidation of interactors of the pro-fusion proteins MFN1 and MFN2 sheds light on novel pathways regulating mitochondrial morphology in apoptosis. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:29447

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Deposited on : 2013-08-26

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