AutophagyJul 31, 2026

Mitochondrial cleanup in neurodegeneration: interaction between parkin-dependent and independent pathways

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Mitochondrial dysfunction is implicated in the pathogenesis of neurodegenerative diseases.

Mitophagy is crucial for maintaining mitochondrial integrity and metabolic balance in neurons.
The review details the PINK1-PRKN/parkin-dependent mitophagy pathway and other PRKN-independent mechanisms.
Various mitophagy pathways, including ubiquitin-dependent and receptor-mediated routes, can intersect and compensate for each other.
Dysregulated mitophagy may contribute to the onset and progression of neurodegenerative diseases.
Understanding the dynamics of these pathways may reveal new therapeutic targets for clinical intervention.

Simplified

Mitochondrial quality control is essential for cellular homeostasis, particularly in neurons, where mitochondrial dysfunction is implicated in the pathogenesis of neurodegenerative diseases. Mitophagy, the selective degradation of damaged or superfluous mitochondria, plays a central role in maintaining mitochondrial integrity and metabolic balance. This review provides a comprehensive overview of the best-characterized PINK1-PRKN/parkin-dependent mitophagy pathway and the expanding repertoire of PRKN-independent mechanisms, including additional ubiquitin-dependent, receptor-mediated, and lipid-mediated pathways. We explore how these pathways intersect and compensate for one another, highlighting the complexity and adaptability of mitochondrial quality control networks. Furthermore, we discuss how dysregulated mitophagy contributes to the onset and progression of neurodegenerative diseases. By examining the interplay between mitophagy pathways and their regulation under physiological and pathological conditions, this review underscores the therapeutic potential of targeting mitophagy in neurodegeneration. Future studies should aim to decode the spatiotemporal dynamics of these pathways to uncover novel opportunities for clinical intervention.

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Mitochondrial cleanup in neurodegeneration: interaction between parkin-dependent and independent pathways

Abstract

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