Regulation of Mitochondrial Integrity, Autophagy and Cell Survival by BNIP3

Kristin Tracy and Kay F. Macleod

volume 3 | issue 6

November/December 2007
Pages: 616 - 619

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

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.

Addendum to:
BNIP3 is an RB/E2F Target Gene Required for Hypoxia-Induced Autophagy
K. Tracy, B.C. Dibling, BT. Spike, J. Knabb, P. Schumacker and K.F. Macleod
Mol Cell Biol 2007; In press

Authors

Kristin Tracy

University of Chicago

Kay F. Macleod

University of Chicago

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: