期刊
AUTOPHAGY
卷 10, 期 6, 页码 1105-1119出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.28615
关键词
PARK2 translocation; BECN1; mitophagy; mitochondrial dynamics; MFN2
类别
资金
- Estonian Research Council [IUT2-5, PUT513]
- European Community
- European Regional Development Fund
- MOBILITAS [MJD120]
The autophagy protein BECN1/Beclin 1 is known to play a central role in autophagosome formation and maturation. The results presented here demonstrate that BECN1 interacts with the Parkinson disease-related protein PARK2. This interaction does not require PARK2 translocation to mitochondria and occurs mostly in cytosol. However, our results suggest that BECN1 is involved in PARK2 translocation to mitochondria because loss of BECN1 inhibits CCCP- or PINK1 over-expression-induced PARK2 translocation. Our results also demonstrate that the observed PARK2-BECN1 interaction is functionally important. Measurements of the level of MFN2 (mitofusin 2), a PARK2 substrate, demonstrate that depletion of BECN1 prevents PARK2 translocation-induced MFN2 ubiquitination and loss. BECN1 depletion also rescues the MFN2 loss-induced suppression of mitochondrial fusion. In sum, our results demonstrate that BECN1 interacts with PARK2 and regulates PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to autophagosome formation.
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