Regulation and roles of mammalian mitophagy.

Mitophagy in mammals proceeds through multiple pathways, including PINK1–Parkin-dependent routes and PINK1/Parkin-independent routes, with coordinated regulation that remains context-dependent.

• Why it matters: Mitochondrial damage is highly detrimental, yet the physiological roles and specific conditions governing different mitophagy pathways in mammals are poorly defined.
• What they did: This Review summarizes current understanding of PINK1–Parkin-dependent and independent mitophagy pathways, focusing on mechanistic distinctions and coordinated regulation, and discusses triggers and therapeutic potential.
• The result: The synthesis clarifies how mitophagy may be activated by physiological and pathological triggers and highlights expanding therapeutic potential from targeting mitophagy in disease.

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