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. 2007 Nov-Dec;3(6):616-9.
doi: 10.4161/auto.4892. Epub 2007 Aug 15.

Regulation of mitochondrial integrity, autophagy and cell survival by BNIP3

Kristin Tracy  1 , Kay F Macleod
Affiliations

Regulation of mitochondrial integrity, autophagy and cell survival by BNIP3

Kristin Tracy et al. Autophagy. 2007 Nov-Dec.

Abstract

Understanding the role of BNIP3 in the systemic response to hypoxia has been complicated by conflicting results that indicate on the one hand that BNIP3 promotes cell death, and other data, including our own that BNIP3 is not sufficient for cell death, but rather plays a critical role in hypoxia-induced autophagy. This work suggests that rather than promoting death, BNIP3 may actually allow survival either by preventing ATP depletion or by eliminating damaged mitochondria. However, the function of BNIP3 may be subverted under unusual conditions associated with acidosis that arise following extended periods of hypoxia and anaerobic glycolysis. Despite this novel insight into BNIP3 function, much remains to be done in terms of pinning down a molecular activity for BNIP3 that explains both its role in autophagy and how this may be subverted to induce cell death. As a target of the RB tumor suppressor, our work also places BNIP3 at the center of efforts to exploit autophagy to better treat human cancers in which tumor hypoxia is implicated as a progression factor.

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Figures

Figure 1
Figure 1
Three different models to explain the function of BNIP3 in autophagy. Model 1 proposes that BNIP3 dimerization and integration into the outer mitochondrial membrane induces damage to mitochondria that results in autophagic cell death. Model 2 proposes that BNIP3 dimers target mitochondria to the autophagosome for degradation by mediating an interaction with an unknown binding partner at the phagophore. Model 3 proposes that BNIP3 promotes autophagy by titrating Bcl-2, a known BNIP3 interacting factor, away from Beclin-1, thereby releasing Beclin-1 to interact with Class III PI-3 kinases at the endoplasmic reticulum to promote initiation of autophagy.
See this image and copyright information in PMC

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