How a damaged mitochondrion is tagged
Mitophagy is the selective clearance of defective mitochondria. The best-characterized route is the PINK1 and Parkin pathway. In a healthy mitochondrion, the kinase PINK1 is imported and rapidly degraded. When the inner membrane potential collapses, PINK1 can no longer be imported and instead builds up on the outer membrane.
Accumulated PINK1 recruits and activates Parkin, an E3 ubiquitin ligase. Parkin attaches ubiquitin chains to outer membrane proteins, marking the whole organelle for disposal.
From label to lysosome
The ubiquitin tags are read by autophagy receptors such as optineurin and NDP52, which bridge the mitochondrion to the growing autophagosome membrane through LC3. The autophagosome engulfs the organelle and then fuses with a lysosome, where acid hydrolases break it down.
Beyond clearing junk, this process limits the spread of reactive oxygen species and faulty mitochondrial DNA. Impaired mitophagy is studied in Parkinson disease, since PINK1 and Parkin mutations are linked to inherited forms of it.