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Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes
Journal article   Peer reviewed

Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes

Youngil Lee, Hwa-Youn Lee, Rita A. Hanna and Asa B. Gustafsson
American Journal of Physiology. Heart and Circulatory Physiology (Print), Vol.301, pp.H1924-H1931
301
2011
DOI: https://doi.org/10.1152/ajpheart.00368.2011
PMCID: PMC3213962
PMID: 21890690
Web of Science ID: WOS:000296716900020

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Abstract

The Bcl2/adenovirus E1B19-kDa interacting protein 3 (Bnip3) is an atypical BH3-only protein that is associated with mitochondrial dysfunction and cell death.Bnip3 is also a potent inducer of mitochondrial autophagy, and in this study we have investigated the mechanisms by which Bnip3 induces autophagy in cardiac myocytes. We found that Bnip3 induced mitochondrial translocation of dynamin-related protein 1 (Drp1), a protein involved in mitochondrial fission in adult myocytes. Drp1-mediatedmitochondrial fission correlated with increased autophagy, and inhibition of Drp1 reduced Bnip3-mediated autophagy. Overexpression of Drp1K38E, a dominant negative of Drp1, or mitofusin 1 prevented mitochondrial fission and autophagy by Bnip3. Also, inhibition of mitochondrial fission or autophagy resulted in increased death of myocytes overexpressing Bnip3. Moreover, Bnip3 promoted translocation of the E3 ubiquitin ligase Parkin to mitochondria, which was prevented in the presence of a Drp1 inhibitor. Interestingly, induction of autophagy by Bnip3 was reduced in Parkin-deficient myocytes. Thus our data suggest that induction of autophagy in response toBnip3 is a protective response activated by the cell that involvesDrp1-mediated mitochondrial fission and recruitment of Parkin.

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