| Autor: |
Bhujabal, Zambarlal, Birgisdottir, Åsa B, Sjøttem, Eva, Brenne, Hanne B, Øvervatn, Aud, Habisov, Sabrina, Kirkin, Vladimir, Lamark, Trond, Johansen, Terje |
| Zdroj: |
EMBO Reports; Jun2017, Vol. 18 Issue 6, p947-961, 15p |
| Abstrakt: |
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, BNIP3, FUNDC1, and Bcl2-L13 recruit ATG8 proteins ( LC3/ GABARAP) to mitochondria during mitophagy. FKBP8 (also known as FKBP38), a unique member of the FK506-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 FKBP8 as an ATG8-interacting protein. Here, we map an N-terminal LC3-interacting region ( LIR) motif in FKBP8 that binds strongly to LC3A both in vitro and in vivo. FKBP8 efficiently recruits lipidated LC3A to damaged mitochondria in a LIR-dependent manner. The mitophagy receptors BNIP3 and NIX in contrast are unable to mediate an efficient recruitment of LC3A even after mitochondrial damage. Co-expression of FKBP8 with LC3A profoundly induces Parkin-independent mitophagy. Strikingly, even when acting as a mitophagy receptor, FKBP8 avoids degradation by escaping from mitochondria. In summary, this study identifies novel roles for FKBP8 and LC3A, which act together to induce mitophagy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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