MIEF1 (mitochondrial elongation factor 1) is a mitochondrial outer membrane protein that regulates mitochondrial dynamics by controlling the recruitment and activity of dynamin-related protein 1 (DRP1) 1. MIEF1 recruits DRP1 to mitochondria independently of FIS1 and MFF 1, and regulates DRP1 GTPase activity and oligomerization through ADP binding 1. Functionally, MIEF1 promotes mitochondrial fission in response to mechanical cues and metabolic demands. Elevated MIEF1 paradoxically induces mitochondrial fusion while inhibiting DRP1 activity, whereas MIEF1 depletion causes fragmentation 1. MIEF1 phosphorylation by actomyosin tension limits DRP1 recruitment and mitochondrial fission, functioning as a mechanotransduction mechanism 2. DRP1- and MIEF1-dependent fission regulates YAP/TAZ, SREBP1/2, and NRF2 transcription factors controlling proliferation, lipogenesis, antioxidant metabolism, and chemotherapy resistance 2. Beyond fission-fusion dynamics, MIEF1 loss impairs mitochondrial respiration, increases oxidative stress, and sensitizes cells to BAX-mediated apoptosis and PINK1-PRKN-dependent mitophagy 3. MIEF1 mutations cause optic atrophy 14, highlighting clinical significance 1. These findings establish MIEF1 as a critical integrator of mechanical signaling, mitochondrial quality control, and cellular fate determination.