The role of energy deficit in autophagy failure in Parkinson's disease.

Mitochondrial complex I dysfunction, ATP depletion, and impaired autophagy are key features of Parkinson's disease (PD), but their causal relationship remains unclear. Although energy stress induces autophagy, autophagy execution requires ATP. Available evidence suggests a biphasic effect of ATP depletion on autophagy in PD, with mild early energy decline promoting autophagy and more severe ATP loss, below a critical threshold, suppressing its completion. This mechanism may contribute to the accumulation of dysfunctional mitochondria and other undegraded cargo, creating a vicious cycle in which mitochondrial dysfunction, ATP decline, and autophagy failure progressively reinforce one another in PD. Here, we review current evidence linking cellular energy status to autophagic dysfunction in PD and discuss its pathogenic and therapeutic implications.