Abstract
BNIP3 and NIX are proteins related to the BH3-only family, which induce both cell death and autophagy. Consistent with their ability to induce cell death, BNIP3 and NIX are implicated in the pathogenesis of cancer and heart disease. In tumor cells, BNIP3 and NIX are regulated by hypoxia, and the deregulation of BNIP3 or NIX expression is associated with tumor growth. In heart muscle, BNIP3 and NIX are regulated by hypoxia and Gαq-dependent signaling, respectively, and their expression is associated with decreased myocardial function. Apart from their role in cell death, BNIP3 and NIX are also implicated in the induction of autophagy. In erythroid cells, NIX is required for a specialized type of autophagy that targets mitochondria for elimination (mitophagy). Similarly, BNIP3 regulates mitophagy in response to hypoxia. In this review, we will discuss possible mechanisms by which BNIP3 and NIX induce cell death and mitophagy. We will also consider the potential relationship between cell death pathways and autophagy in development and homeostasis.
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Abbreviations
- Atg1:
-
autophagy-related 1
- BNIP3:
-
BCL2 and adenovirus E1B 19 kDa-interacting protein 3
- LC3:
-
microtubule-associated protein 1 light chain 3
- MPTP:
-
mitochondrial permeability transition pore
- NIX:
-
NIP3-like protein X
- ULK1:
-
Unc51-like kinase
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This research was supported by a grant from the National Institutes of Health to PAN (R21 DK074519), and by the American, Lebanese, and Syrian Associated Charities.
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Zhang, J., Ney, P. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16, 939–946 (2009). https://doi.org/10.1038/cdd.2009.16
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DOI: https://doi.org/10.1038/cdd.2009.16
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