Role of BNIP3 and NIX in cell death, autophagy, and mitophagy

Cell Death Differ. 2009 Jul;16(7):939-46. doi: 10.1038/cdd.2009.16. Epub 2009 Feb 20.


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 Galphaq-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Cell Death / physiology
  • Cell Hypoxia / physiology
  • Heart Diseases / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mitochondria / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • BNIP3 protein, human
  • BNIP3L protein, human
  • BNip3 protein, mouse
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nix protein, mouse
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins