Mitophagy is the selective autophagy of damaged mitochondria. In the context of cell injury, which protein complex acts as the primary sensor that tags damaged mitochondria for mitophagic degradation?
- A BCL-2/BCL-XL complex
- B mTOR complex 1 (mTORC1) on intact mitochondrial outer membrane
- C PINK1/Parkin pathway — PINK1 stabilizes on depolarized mitochondria and recruits Parkin E3 ubiquitin ligase ✓
- D p62/sequestosome-1 binding directly to cytochrome c
Explanation
PINK1 (PTEN-induced kinase 1) is normally imported into healthy mitochondria and degraded. When mitochondrial membrane potential (ΔΨm) is lost after injury, PINK1 accumulates on the outer mitochondrial membrane and phosphorylates ubiquitin and Parkin, recruiting the E3 ligase Parkin. Parkin ubiquitinates outer membrane proteins, which are recognized by autophagy receptors (optineurin, NDP52) that link to LC3 on autophagosomes. Loss of function mutations in PINK1 and Parkin are associated with autosomal recessive Parkinson disease due to impaired clearance of damaged mitochondria.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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