PINK1-phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria

Yun Chen, Gerald W. Dorn

Research output: Contribution to journalArticle

518 Citations (Scopus)

Abstract

Senescent and damaged mitochondria undergo selective mitophagic elimination through mechanisms requiring two Parkinson's disease factors, the mitochondrial kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the PINK-Parkin interaction and the identity of key factors directing Parkin to damaged mitochondria are unknown. We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. Ablation of Mfn2 in mouse cardiac myocytes prevented depolarization-induced translocation of Parkin to the mitochondria and suppressed mitophagy. Accumulation of morphologically and functionally abnormal mitochondria induced respiratory dysfunction in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes, causing dilated cardiomyopathy. Thus, Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria.

Original languageEnglish (US)
Pages (from-to)471-475
Number of pages5
JournalScience
Volume340
Issue number6131
DOIs
StatePublished - Apr 26 2013
Externally publishedYes

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Mitochondria
Cardiac Myocytes
Mitochondrial Degradation
PTEN Phosphohydrolase
Guanosine
Dilated Cardiomyopathy
Mitochondrial Membranes
Ligases
Ubiquitin
Quality Control
Drosophila
Phosphotransferases
Fibroblasts
Proteins

ASJC Scopus subject areas

  • General

Cite this

PINK1-phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria. / Chen, Yun; Dorn, Gerald W.

In: Science, Vol. 340, No. 6131, 26.04.2013, p. 471-475.

Research output: Contribution to journalArticle

Chen, Yun ; Dorn, Gerald W. / PINK1-phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria. In: Science. 2013 ; Vol. 340, No. 6131. pp. 471-475.
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