Mitophagy in the pathogenesis and management of disease

  • Cell Res. 2026 Jan;36(1):11-37. doi: 10.1038/s41422-025-01203-7.
Qi Wang  #  1 ,  Yu Sun  #  2 ,  Terytty Yang Li  3 ,  Johan Auwerx  4
Affiliations
  • 1. Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • 2. Shanghai Key Laboratory of Metabolic Remodeling and Health, Laboratory of Longevity and Metabolic Adaptations, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • 3. Shanghai Key Laboratory of Metabolic Remodeling and Health, Laboratory of Longevity and Metabolic Adaptations, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China. [email protected].
  • 4. Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. [email protected].
  • # Contributed equally.
PMID: 41486294 DOI: 10.1038/s41422-025-01203-7
Abstract

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.