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FKBP8 recruits LC3A to mediate Parkin‐independent mitophagy
Author(s) -
Bhujabal Zambarlal,
Birgisdottir Åsa B,
Sjøttem Eva,
Brenne Hanne B,
Øvervatn Aud,
Habisov Sabrina,
Kirkin Vladimir,
Lamark Trond,
Johansen Terje
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643147
Subject(s) - mitophagy , parkin , fkbp , autophagy , microbiology and biotechnology , mitochondrion , biology , ubiquitin , receptor , biochemistry , apoptosis , gene , medicine , disease , parkinson's disease
Mitophagy, the selective removal of damaged or excess mitochondria by autophagy, is an important process in cellular homeostasis. The outer mitochondrial membrane ( OMM ) proteins NIX , BNIP 3, FUNDC 1, and Bcl2‐L13 recruit ATG 8 proteins ( LC 3/ GABARAP ) to mitochondria during mitophagy. FKBP 8 (also known as FKBP 38), a unique member of the FK 506‐binding protein ( FKBP ) family, is similarly anchored in the OMM and acts as a multifunctional adaptor with anti‐apoptotic activity. In a yeast two‐hybrid screen, we identified FKBP 8 as an ATG 8‐interacting protein. Here, we map an N‐terminal LC 3‐interacting region ( LIR ) motif in FKBP 8 that binds strongly to LC 3A both in vitro and in vivo . FKBP 8 efficiently recruits lipidated LC 3A to damaged mitochondria in a LIR ‐dependent manner. The mitophagy receptors BNIP 3 and NIX in contrast are unable to mediate an efficient recruitment of LC 3A even after mitochondrial damage. Co‐expression of FKBP 8 with LC 3A profoundly induces Parkin‐independent mitophagy. Strikingly, even when acting as a mitophagy receptor, FKBP 8 avoids degradation by escaping from mitochondria. In summary, this study identifies novel roles for FKBP 8 and LC 3A, which act together to induce mitophagy.