ROLE OF BNIP3 AND NIX IN CELL DEATH, AUTOPHAGY, AND MITOPHAGY

By Ji Zhang, P. Ney. Cell Death and Differentiation, 2009

972 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Molecular Biology, Parasitology

View Paper: https://www.semanticscholar.org/paper/d19ec3542dce28b974c4bfd374fa80d6b00c992a

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In Epidemiology

1. Beth Levine
2. Douglas R. Green
3. T. Johansen
4. T. Lamark
5. Ivan Dikic
6. Yan Pang
7. Xianqun Fan
8. Xieyang Xu

In Molecular Biology

1. Beth Levine
2. Douglas R. Green
3. T. Johansen
4. T. Lamark
5. Ivan Dikic
6. Yan Pang
7. Xianqun Fan
8. Xieyang Xu

In Parasitology

1. Douglas R. Green
2. Beth Levine
3. Yan Pang
4. Xianqun Fan
5. Xieyang Xu
6. Ivan Dikic
7. T. Lamark
8. T. Johansen

Citations in the corpus

• The LIR motif – crucial for selective autophagy (2013, background): “Two homologous BCL2 homology 3 (BH3)only proteins, Bnip3 and Nix (also known as Bnip3L), are able to induce mitophagy and can also activate cell death (reviewed by Zhang and Ney, 2009).”
• Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances (2025, positive): “68 Of note, the BNIP3/NIX pathway was speci fi cally up-regulated when mitochondrial oxidative stress was generated in the hypoxic environment to further induce mitophagy.”
• Nix is a selective autophagy receptor for mitochondrial clearance (2010, background): “The mitochondrion-localized proteins Bcl2/E1B 19 kDa-interacting protein 3-like protein (BNIP3) and Nix (also known as BNIP3L) have been implicated in the removal of mitochondria during an autophagic response”
• To be or not to be? How selective autophagy and cell death govern cell fate. (2014, positive): “These proteins may act to directly recruit the autophagy machinery to the mitochondria (Zhang and Ney, 2009) and may also promote mitophagy through interaction with Bcl-2, an antiapoptotic protein (see below) that resides on the mitochondrial outer membrane.”