Hypoxia is really a decrease in the normal level of tissue oxygen tension and is just a important feature of solid tumours where it occurs due to an inadequate blood flow. Hypoxia evokes a selection of adaptive changes in cells that facilitate survival under low oxygen conditions. The transcription factor hypoxia inducible factor1a is stabilised in reaction to hypoxia where it combines with HIF 1b to make a 850649-61-5 Alogliptin energetic HIF 1 heterodimer. HIF 1 binds to hypoxia response components in a diverse selection of target genes such as the Bcl 2 family members BNIP3 and, its homologue, BNIP3L. The Bcl 2 family of proteins play a critical role in the regulation of apoptosis. Members of this family share up to four homologous regions, named Bcl 2 homology domains. Antiapoptotic people including Bcl 2, Bcl xL, Bcl w, A1 and Mcl 1 include all Lymph node BH domains and generally reside at the outer mitochondrial membrane, where they integrate via a transmembrane domain. The antiapoptotic members bind to and prevent two sets of professional apoptotic Bcl 2 family proteins. The very first group of pro apoptotic people, termed the BH3 only proteins, include BAD, BID, BIK, BIM, BNIP3, BNIP3L? HRK, NOXA and PUMA. These are transcriptionally induced and/or posttranslationally activated in reaction to specific stress stimuli. The next professional apoptotic group, or effectors, including BAK and BAX? induce apoptosis via pore formation in the mitochondria ultimately causing cytochrome c release, APAF1 initiation and caspase activation. Bcl 2 and Bcl xL also regulate autophagy, the sequestration and destruction of cytoplasmic contents in vacuoles via the lysosome, by binding to and inhibiting oral Hedgehog inhibitor Beclin 1 to the BH3only autophagy activator. Some other BH3 only proteins have now been shown to activate autophagy via binding to Bcl 2/Bcl xL and releasing Beclin 1. The function of BNIP3 in the hypoxia response remains controversial. Many of the early studies implicated BNIP3 being an inducer of cell death and the more recent work of Gibson and colleagues supports this. Nevertheless, other organizations have found no pro death aftereffect of BNIP3 and most cultured cells can tolerate extended periods of hypoxia without negative effects, despite expression of BNIP3. Several groups have implicated BNIP3 as having an immediate or indirect role in hypoxia caused autophagy or mitophagy. However, this is also questionable, as yet another study indicated that hypoxia induced autophagy occurs independently of BNIP3 and BNIP3L expression. Whilst the majority of Bcl 2 family members are regulated posttranslationally, we hypothesised that BNIP3 may also be susceptible to this form of control. A better comprehension of the system of control of BNIP3 might explain the controversy surrounding the protein and help to clarify its role in the reaction to hypoxia.