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Biochim Biophys Acta. 2015 Oct;1853(10 Pt B):2797-801. doi: 10.1016/j.bbamcr.2015.01.013. Epub 2015 Jan 26.

Autophagy machinery in the context of mammalian mitophagy.

Author information

1
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
2
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: nmizu@m.u-tokyo.ac.jp.

Abstract

Autophagy is an intracellular catabolic system that degrades cytoplasmic proteins and organelles. Damaged mitochondria can be degraded by a selective type of autophagy, which is termed mitophagy. PINK1-Parkin-dependent mitophagy has been extensively studied in the mammalian system. PINK1 accumulates on damaged mitochondria to recruit Parkin, which subsequently ubiquitinates a broad range of outer mitochondrial membrane proteins. Ubiquitinated mitochondria associate with the autophagosome formation site, and are selectively incorporated into autophagosomes. During this process, damaged mitochondria first associate with the autophagosome formation site together with upstream autophagy factors, then are efficiently incorporated into autophagosomes through binding with autophagosome adaptors. This "two-step model" may be applied to other selective types of autophagy.

KEYWORDS:

Mitophagy; Parkin; Selective autophagy; Two-step model

PMID:
25634658
DOI:
10.1016/j.bbamcr.2015.01.013
[Indexed for MEDLINE]
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