BNIP3 Protein Suppresses PINK1 Kinase Proteolytic Cleavage to Promote Mitophagy

Zhang, Tongmei; Xue, Liang; Li, Li; Tang, Chengyuan; Wan, Zhengqing; Wang, Ruoxi; Tan, Jieqiong; Tan, Ya; Han, Hailong; Tian, Runyi; Billiar, Timothy R.; Tao, W. Andy; Zhang, Zhuohua

doi:10.1074/jbc.m116.733410

Cited by 210 publications

(159 citation statements)

References 55 publications

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“…Initiation of autophagy is regulated by various signals including mTORC1 signaling, AMPK activation, and expression of regulatory proteins such as REDD1 and BCL2/Adenovirus E1B 19kDa Interacting Protein 3 (BNIP3) (Gordon et al, 2014, Kim, Kundu et al, 2011, Qiao, Dennis et al, 2015, Zhang, Xue et al, 2016). For instance, mTORC1 phosphorylates several proteins such as uncoordinated like kinase 1 (ULK1) to inhibit the initiation steps of autophagy (Kim et al, 2011).…”

Section: 1 Regulation Of Protein Balancementioning

confidence: 99%

Androgen-mediated regulation of skeletal muscle protein balance

Rossetti

Steiner

Gordon

2017

Molecular and Cellular Endocrinology

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Androgens significantly alter muscle mass in part by shifting protein balance in favor of net protein accretion. During various atrophic conditions, the clinical impact of decreased production or bioavailability of androgens (termed hypogonadism) is important as a loss of muscle mass is intimately linked with survival outcome. While androgen replacement therapy increases muscle mass in part by restoring protein balance, this is not a comprehensive treatment option due to potential side effects. Therefore, an understanding of the mechanisms by which androgens alter protein balance is needed for the development of androgen-independent therapies. While the data in humans suggest androgens alter protein balance (both synthesis and breakdown) in the fasted metabolic state, a predominant molecular mechanism(s) behind this observation is still lacking. This failure is likely due in part to inconsistent experimental design between studies including failure to control nutrient/feeding status, the method of altering androgens, and the model systems utilized.

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Section: 1 Regulation Of Protein Balancementioning

confidence: 99%

Androgen-mediated regulation of skeletal muscle protein balance

Rossetti

Steiner

Gordon

2017

Molecular and Cellular Endocrinology

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“…The mitophagy receptor BNIP3 was shown to interact with Pink1 and to inhibit its proteolytic degradation (Zhang et al, 2016). Thereby the uncleaved form of Pink1 is stabilized, which can promote the induction of Parkin-dependent mitophagy.…”

Section: Regulation Of Pink1/parkin Mitophagy and Crosstalk To Other mentioning

confidence: 99%

“…In cardiomyocytes, it induces mitochondrial translocation of the fission factor Drp1 leading to fragmentation and subsequent induction of Pink1/Parkin-mediated mitophagy (explained in a latter section in detail) through translocation of Parkin to mitochondria. Furthermore, BNIP3-induced mitophagy is reduced in Parkin-deficient cells (Lee et al, 2011), and BNIP3 can stabilize Pink1, the sensor kinase of Pink1/Parkin-mediated mitophagy (Zhang et al, 2016), linking the receptor-mediated with the Pink1/Parkinmediated pathway. BNIP3 is regulated by phosphorylation by a yet unknown kinase at Ser17 and Ser24, residues flanking the LIR, which enhances its binding to the Atg8 protein LC3B and the SNARE GATE-16 (Zhu et al, 2013).…”

Section: Nix (Bnip3l) and Bnip3mentioning

confidence: 99%

How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways

Zimmermann

Reichert

2017

Biological Chemistry

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Mitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/ membranes and DNA. To cope with this and other sorts of organellar stress, a multi-level quality control system exists to maintain cellular homeostasis. One critical level of mitochondrial quality control is the removal of damaged mitochondria by mitophagy. This process utilizes parts of the general autophagy machinery, e.g. for the formation of autophagosomes but also employs mitophagy-specific factors. Depending on the proteins utilized mitophagy is divided into receptor-mediated and ubiquitin-mediated mitophagy. So far, at least seven receptor proteins are known to be required for mitophagy under different experimental conditions. In contrast to receptor-mediated pathways, the Pink-Parkin-dependent pathway is currently the best characterized ubiquitin-mediated pathway. Recently two additional ubiquitin-mediated pathways with distinctive similarities and differences were unraveled. We will summarize the current state of knowledge about these multiple pathways, explain their mechanism, and describe the regulation and crosstalk between these pathways. Finally, we will review recent evidence for the evolutionary conservation of ubiquitin-mediated mitophagy pathways.

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“…Indeed, we observed increased expression of BNIP3, a receptor for mitophagy, as a defensive response against defective mitochondria (44, 45) because BNIP3 overexpression induces autophagy in skeletal muscle in vivo (53). Expression of Bnip3 in Drosophila also suppresses muscle degeneration and the mitochondrial abnormality caused by PINK1 inactivation (46). …”

Section: Discussionmentioning

confidence: 99%

Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle

et al. 2018

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Apobec2 is a member of the activation-induced deaminase/apolipoprotein B mRNA editing enzyme catalytic polypeptide cytidine deaminase family expressed in differentiated skeletal and cardiac muscle. We previously reported that Apobec2 deficiency in mice leads to a shift in muscle fiber type, myopathy, and diminished muscle mass. However, the mechanisms of myopathy caused by Apobec2 deficiency and its physiologic functions are unclear. Here we show that, although Apobec2 localizes to the sarcomeric Z-lines in mouse tissue and cultured myotubes, the sarcomeric structure is not affected in Apobec2-deficient muscle. In contrast, electron microscopy reveals enlarged mitochondria and mitochondria engulfed by autophagic vacuoles, suggesting that Apobec2 deficiency causes mitochondrial defects leading to increased mitophagy in skeletal muscle. Indeed, Apobec2 deficiency results in increased reactive oxygen species generation and depolarized mitochondria, leading to mitophagy as a defensive response. Furthermore, the exercise capacity of Apobec2−/− mice is impaired, implying Apobec2 deficiency results in ongoing muscle dysfunction. The presence of rimmed vacuoles in myofibers from 10-mo-old mice suggests that the chronic muscle damage impairs normal autophagy. We conclude that Apobec2 deficiency causes mitochondrial defects that increase muscle mitophagy, leading to myopathy and atrophy. Our findings demonstrate that Apobec2 is required for mitochondrial homeostasis to maintain normal skeletal muscle function.—Sato, Y., Ohtsubo, H., Nihei, N., Kaneko, T., Sato, Y., Adachi, S.-I., Kondo, S., Nakamura, M., Mizunoya, W., Iida, H., Tatsumi, R., Rada, C., Yoshizawa, F. Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle.

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BNIP3 Protein Suppresses PINK1 Kinase Proteolytic Cleavage to Promote Mitophagy

Cited by 210 publications

References 55 publications

Androgen-mediated regulation of skeletal muscle protein balance

Androgen-mediated regulation of skeletal muscle protein balance

How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways

Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle

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