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Zhang, T., Xue, L., Li, L., Tang, C., Wan, Z., Wang, R., Tan, J., Tan, Y., Han, H., Tian, R., Billiar, T.R., Tao, W.A., Zhang, Z. (2016). BNIP3 Protein Suppresses PINK1 Kinase Proteolytic Cleavage to Promote Mitophagy.  J. Biol. Chem. 291(41): 21616--21629.
FlyBase ID
FBrf0233946
Publication Type
Research paper
Abstract

Mutations in PINK1 (PTEN-induced putative kinase 1) cause early onset familial Parkinson's disease (PD). PINK1 accumulates on the outer membrane of damaged mitochondria followed by recruiting parkin to promote mitophagy. Here, we demonstrate that BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a mitochondrial BH3-only protein, interacts with PINK1 to promote the accumulation of full-length PINK1 on the outer membrane of mitochondria, which facilitates parkin recruitment and PINK1/parkin-mediated mitophagy. Inactivation of BNIP3 in mammalian cells promotes PINK1 proteolytic processing and suppresses PINK1/parkin-mediated mitophagy. Hypoxia-induced BNIP3 expression results in increased expression of full-length PINK1 and mitophagy. Consistently, expression of BNIP3 in Drosophila suppresses muscle degeneration and the mitochondrial abnormality caused by PINK1 inactivation. Together, the results suggest that BNIP3 plays a vital role in regulating PINK1 mitochondrial outer membrane localization, the proteolytic process of PINK1 and PINK1/parkin-mediated mitophagy under physiological conditions. Functional up-regulation of BNIP3 may represent a novel therapeutic strategy to suppress the progression of PD.

PubMed ID
PubMed Central ID
PMC5076832 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference
    Alleles (5)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (4)