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.