Basak Bishal, Holzbaur Erika L F
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
J Mol Biol. 2025 Sep 15;437(18):169161. doi: 10.1016/j.jmb.2025.169161. Epub 2025 Apr 21.
Mitochondrial quality control is instrumental in regulating neuronal health and survival. The receptor-mediated clearance of damaged mitochondria by autophagy, known as mitophagy, plays a key role in controlling mitochondrial homeostasis. Mutations in genes that regulate mitophagy are causative for familial forms of neurological disorders including Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). PINK1/Parkin-dependent mitophagy is the best studied mitophagy pathway, while more recent work has brought to light additional mitochondrial quality control mechanisms that operate either in parallel to or independent of PINK1/Parkin mitophagy. Here, we discuss our current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis. We also summarize progress in our understanding of the links between mitophagic dysfunction and neurodegeneration, and highlight the potential for therapeutic interventions to maintain mitochondrial health and neuronal function.
线粒体质量控制对调节神经元健康和存活至关重要。通过自噬介导的受损线粒体清除，即线粒体自噬，在控制线粒体稳态中起关键作用。调节线粒体自噬的基因突变是包括帕金森病（PD）和肌萎缩侧索硬化症（ALS）在内的家族性神经疾病的病因。PINK1/帕金蛋白依赖性线粒体自噬是研究最深入的线粒体自噬途径，而最近的研究揭示了其他与PINK1/帕金蛋白依赖性线粒体自噬并行或独立运作的线粒体质量控制机制。在此，我们讨论目前对神经元中线粒体自噬机制以维持线粒体稳态的理解。我们还总结了在理解线粒体自噬功能障碍与神经退行性变之间联系方面的进展，并强调了通过治疗干预来维持线粒体健康和神经元功能的潜力。
