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Doctoral thesis
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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

ContributorsPyakurel, Aswin
Defense date2013-08-08
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.

eng
Citation (ISO format)
PYAKUREL, Aswin. Elucidation of interactors of the pro-fusion proteins MFN1 and MFN2 sheds light on novel pathways regulating mitochondrial morphology in apoptosis. 2013. doi: 10.13097/archive-ouverte/unige:29447
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Creation08/21/2013 10:31:00 AM
First validation08/21/2013 10:31:00 AM
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