Phylogenetic Footprinting of Mitochondrial Vulnerability: Linking Ancient α-

The endosymbiotic origin of mitochondria from an α-proteobacterial ancestor is a settled fact of evolutionary biology. However, the functional implications of this ancestry for human disease, particularly neurodegenerative disorders characterized by systemic mitochondrial failure such as Alzheimer's disease (AD) and Parkinson's disease (PD), remain almost entirely unmapped. Current research treats mitochondrial dysfunction as a proximate, monolithic endpoint, neglecting the discrete, evolutionarily-conserved subsystems—each with independent phylogenetic histories—that may fail selectively under specific stresses. We hypothesize that pathogenic energetic collapse in neurons arises not randomly, but through the failure of specific, ancient bacterial-origin pathways ill-adapted to the unique pressures of the human neuronal environment over a protracted lifespan.