Wang Qi, Sun Yu, Li Terytty Yang, Auwerx Johan
Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Shanghai Key Laboratory of Metabolic Remodeling and Health, Laboratory of Longevity and Metabolic Adaptations, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
Cell Res. 2026 Jan;36(1):11-37. doi: 10.1038/s41422-025-01203-7. Epub 2026 Jan 5.
Mitophagy, an evolutionarily conserved quality-control process, selectively removes damaged mitochondria to maintain cellular homeostasis. Recent advances in our understanding of the molecular machinery underlying mitophagy - from receptors and stress-responsive triggers to lysosomal degradation - illustrate its key role in maintaining mitochondrial integrity and adapting mitochondrial function to ever-changing physiological demands. In this review, we outline the fundamental mechanisms of mitophagy and discuss how dysregulation of this pathway disrupts mitochondrial function and metabolic balance, driving a wide range of disorders, including neurodegenerative, cardiovascular, metabolic, and immune-related diseases, as well as cancer. We explore the dual role of mitophagy as both a disease driver and a therapeutic target, highlighting the efforts and challenges of translating mechanistic insights into precision therapies. Targeting mitophagy to restore mitochondrial homeostasis may be at the center of a large range of translational opportunities for improving human health.
线粒体自噬是一种进化上保守的质量控制过程,它选择性地清除受损的线粒体以维持细胞内稳态。我们对线粒体自噬基础分子机制的理解取得了新进展,从受体、应激反应触发因素到溶酶体降解,这些进展都表明了线粒体自噬在维持线粒体完整性以及使线粒体功能适应不断变化的生理需求方面的关键作用。在这篇综述中,我们概述了线粒体自噬的基本机制,并讨论了该途径的失调如何破坏线粒体功能和代谢平衡,从而引发多种疾病,包括神经退行性疾病、心血管疾病、代谢性疾病、免疫相关疾病以及癌症。我们探讨了线粒体自噬作为疾病驱动因素和治疗靶点的双重作用,强调了将机制性见解转化为精准疗法的努力和挑战。靶向线粒体自噬以恢复线粒体稳态可能是改善人类健康的众多转化机会的核心。