The pathways of mitophagy for quality control and clearance of mitochondria

G. Ashrafi, T. L. Schwarz

Research output: Contribution to journalReview articlepeer-review

632 Scopus citations

Abstract

Selective autophagy of mitochondria, known as mitophagy, is an important mitochondrial quality control mechanism that eliminates damaged mitochondria. Mitophagy also mediates removal of mitochondria from developing erythrocytes, and contributes to maternal inheritance of mitochondrial DNA through the elimination of sperm-derived mitochondria. Recent studies have identified specific regulators of mitophagy that ensure selective sequestration of mitochondria as cargo. In yeast, the mitochondrial outer membrane protein autophagy-related gene 32 (ATG32) recruits the autophagic machinery to mitochondria, while mammalian Nix is required for degradation of erythrocyte mitochondria. The elimination of damaged mitochondria in mammals is mediated by a pathway comprised of PTEN-induced putative protein kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin. PINK1 and Parkin accumulate on damaged mitochondria, promote their segregation from the mitochondrial network, and target these organelles for autophagic degradation in a process that requires Parkin-dependent ubiquitination of mitochondrial proteins. Here we will review recent advances in our understanding of the different pathways of mitophagy. In addition, we will discuss the relevance of these pathways in neurons where defects in mitophagy have been implicated in neurodegeneration.

Original languageEnglish
Pages (from-to)31-42
Number of pages12
JournalCell Death and Differentiation
Volume20
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • PINK1
  • Parkin
  • mitochondria
  • mitochondrial dynamics
  • mitophagy
  • neuron

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