Mitophagy (PINK1 / Parkin)

What it is

Mitophagy is the selective removal of damaged or excess mitochondria by autophagy. The canonical PINK1/Parkin pathway works as follows:

1. Healthy mitochondria import PINK1 across the inner membrane where it is constitutively degraded.
2. Membrane-potential loss stabilises PINK1 on the outer membrane.
3. PINK1 recruits and activates Parkin (an E3 ubiquitin ligase).
4. Parkin ubiquitinates outer-membrane proteins, marking the organelle for autophagosome capture.

Receptor-mediated mitophagy (BNIP3, NIX, FUNDC1) operates in parallel.

Why it matters in aging

Mitophagy flux declines with age in most tissues. PINK1 and Parkin loss-of-function mutations cause familial Parkinson’s disease, illustrating how mitophagy failure damages neurons over decades.

What activates mitophagy

• Energy stress (AMPK activation).
• Spermidine, urolithin A (best-evidenced supplement for mitophagy).
• Exercise.
• Rapamycin (via general autophagy up-regulation).

Related entries

Disabled macroautophagy, Mitochondrial dysfunction, Urolithin A.