Mitophagy (PINK1 / Parkin)

Definition

Category: Quality-control pathway

Also known as: selective mitochondrial autophagy, PINK1/Parkin pathway

Mitophagy is selective autophagic clearance of mitochondria. In the studied PINK1/Parkin pathway, loss of membrane potential allows PINK1 to accumulate on the outer membrane. PINK1-dependent ubiquitin phosphorylation can recruit and activate the E3 ligase Parkin, promoting mitochondrial protein ubiquitination and clearance in experimental cell systems. Urolithin A has been studied as a mitophagy inducer in worm, cell and rodent experiments; this mechanistic relationship does not establish a human aging benefit.

Key points

• Ryu2016 reports urolithin A-associated mitophagy in experimental models and loss of the worm lifespan response after interference with selected autophagy/mitophagy genes. This does not identify an exclusive direct molecular binding target or prove every human effect is mediated by mitophagy.
• PINK1/Parkin is one experimentally studied route. NIX binds LC3/GABARAP proteins and contributes to mitochondrial clearance in mouse reticulocytes; FUNDC1 interacts with LC3 in hypoxic mouse platelets. These pathways have different experimental and cell contexts.
• Inducing mitophagy in an experimental model or changing a muscle biomarker in a trial does not by itself establish a human aging or lifespan benefit.

Related interventions

• Urolithin A

Sourcing

Narendra2010, DOI10.1371/journal.pbio.1000298; Kane2014, DOI10.1083/jcb.201402104; Novak2010, DOI10.1038/embor.2009.256; Zhang2016, DOI10.7554/eLife.21407; Ryu2016, DOI10.1038/nm.4132. Original experimental sections describe PINK1 stabilization, ubiquitin/Parkin activation, NIX/FUNDC1 receptor examples and urolithin A model context. These are mechanism references, not human clinical approval or an exhaustive pathway ranking.

Reference synthesis (mechanism context, not a human-trial evidence tier).