The yin and yang of neuronal mitophagy: Physiological functions and pathological implications in neurodevelopmental disorders

Maintenance of mitochondrial function is crucial, especially for the energy-demanding and metabolically active neuronal cells. Owing to their post-mitotic nature, neurons are highly vulnerable to mitochondrial dysfunction and therefore rely heavily on mitochondrial quality control mechanisms to mitigate damage and sustain cellular and organismal homeostasis. Mitophagy, the selective autophagic degradation of mitochondria, is the prominent mitochondrial turnover mechanism, required for supporting proper neuronal development and function. Impairment or deregulation of mitophagy pathways has been associated with a wide spectrum of neurological disorders. While mitophagy generally exerts neuroprotective effects, its excessive or uncontrolled activation can be detrimental, potentially leading to neuronal death. This review summarizes the primary pathways involved in neuronal mitophagy and explores their relevance to the etiology and pathophysiology of common neurodevelopmental disorders.