Mitochondrial dynamics (fission and fusion)

Mitochondrial dynamics refers to continuous cycles of fission (division) and fusion (merging) that remodel the mitochondrial network in response to metabolic demands and cellular stress. Fission is driven by DRP1 (dynamin-related protein 1), a cytosolic GTPase recruited to the outer membrane by adaptors MFF and FIS1; outer-membrane fusion requires MFN1 and MFN2 (mitofusins 1 and 2), and inner-membrane fusion requires OPA1 (optic atrophy 1). Fusion allows complementation between partially damaged organelles and sustains oxidative phosphorylation efficiency, whereas fission segregates depolarised segments for clearance by mitophagy via the PINK1–Parkin pathway. Aging is linked to a shift toward fragmentation: reduced DRP1 activity, lower OPA1 levels, and altered MFN2 expression have been documented in aged rodent neurons, skeletal muscle, and oocytes, impairing energy generation and mitochondrial quality control (Sharma et al. 2019). In human age-related diseases including Parkinson's disease, type 2 diabetes, and sarcopenia, fission–fusion imbalance correlates with impaired mitophagy flux and accumulation of dysfunctional mitochondria, though whether the imbalance is a primary driver or secondary consequence of aging in humans remains under active investigation (Liu et al. 2020).