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Receptor-mediated mitophagy in yeast and mammalian systems.

Abstract
Mitophagy, or mitochondria autophagy, plays a critical role in selective removal of damaged or unwanted mitochondria. Several protein receptors, including Atg32 in yeast, NIX/BNIP3L, BNIP3 and FUNDC1 in mammalian systems, directly act in mitophagy. Atg32 interacts with Atg8 and Atg11 on the surface of mitochondria, promoting core Atg protein assembly for mitophagy. NIX/BNIP3L, BNIP3 and FUNDC1 also have a classic motif to directly bind LC3 (Atg8 homolog in mammals) for activation of mitophagy. Recent studies have shown that receptor-mediated mitophagy is regulated by reversible protein phosphorylation. Casein kinase 2 (CK2) phosphorylates Atg32 and activates mitophagy in yeast. In contrast, in mammalian cells Src kinase and CK2 phosphorylate FUNDC1 to prevent mitophagy. Notably, in response to hypoxia and FCCP treatment, the mitochondrial phosphatase PGAM5 dephosphorylates FUNDC1 to activate mitophagy. Here, we mainly focus on recent advances in our understanding of the molecular mechanisms underlying the activation of receptor-mediated mitophagy and the implications of this catabolic process in health and disease.
AuthorsLei Liu, Kaori Sakakibara, Quan Chen, Koji Okamoto
JournalCell research (Cell Res) Vol. 24 Issue 7 Pg. 787-95 (Jul 2014) ISSN: 1748-7838 [Electronic] England
PMID24903109 (Publication Type: Journal Article, Review)
Chemical References
  • ATG8 protein, S cerevisiae
  • Atg11 protein, S cerevisiae
  • Atg32 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • BNIP3 protein, human
  • BNIP3L protein, human
  • FUNDC1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins
  • Vesicular Transport Proteins
  • src-Family Kinases
  • Casein Kinase II
Topics
  • Animals
  • Apoptosis
  • Autophagy-Related Protein 8 Family
  • Autophagy-Related Proteins
  • Casein Kinase II (metabolism)
  • Cell Hypoxia
  • Humans
  • Membrane Proteins (physiology)
  • Microtubule-Associated Proteins (metabolism)
  • Mitochondria (metabolism)
  • Mitochondrial Dynamics (physiology)
  • Mitochondrial Proteins (physiology)
  • Mitophagy
  • Phosphorylation
  • Proto-Oncogene Proteins (physiology)
  • Receptors, Cytoplasmic and Nuclear (biosynthesis, physiology)
  • Saccharomyces cerevisiae (ultrastructure)
  • Saccharomyces cerevisiae Proteins (biosynthesis, metabolism, physiology)
  • Tumor Suppressor Proteins (physiology)
  • Vesicular Transport Proteins (metabolism)
  • src-Family Kinases (metabolism)

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