Selective escape of proteins from the mitochondria during mitophagy

Shotaro Saita, Michiko Shirane, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

Abstract

Mitophagy refers to the degradation of mitochondria by the autophagy system that is regulated by Parkin and PINK1, mutations in the genes for which have been linked to Parkinson's disease. Here we show that certain mitochondrial outer membrane proteins, including FKBP38 and Bcl-2, translocate from the mitochondria to the endoplasmic reticulum (ER) during mitophagy, thereby escaping degradation by autophagosomes. This translocation depends on the ubiquitylation activity of Parkin and on microtubule polymerization. Photoconversion analysis confirmed that FKBP38 detected at the ER during mitophagy indeed represents preexisting protein transported from the mitochondria. The escape of FKBP38 and Bcl-2 from the mitochondria is determined by the number of basic amino acids in their COOH-terminal signal sequences. Furthermore, the translocation of FKBP38 is essential for the suppression of apoptosis during mitophagy. Our results thus show that not all mitochondrial proteins are degraded during mitophagy, with some proteins being evacuated to the ER to prevent unwanted apoptosis.

Original languageEnglish
Article number1410
JournalNature communications
Volume4
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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