Coupled mitochondrial and endoplasmic reticulum membrane failure in Parkinson's disease

Parkinson's disease is usually framed as a dopaminergic and α-synuclein disorder. We propose, as a testable hypothesis, that vulnerable nigral neurons enter disease through coupled physical-state failure of the mitochondrial inner membrane and endoplasmic reticulum, disrupting coenzyme Q10 diffusion, protein import, ER folding, and integrated-stress signalling. The model makes falsifiable biophysical predictions and motivates pharmacological paraoxonase-2 modulation as one therapeutic probe.