We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
BNIP3 mediates cell death by different pathways following localization to endoplasmic reticulum and mitochondrion.
- Authors
Lu Zhang; Li Li; Han Liu; Borowitz, Joseph L.; Isom, Gary E.
- Abstract
BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only proapoptotic member of the Bcl-2 family. Because the interaction of Bcl-2 proteins with intracellular Ca2+ stores has been linked to apoptosis, the role of Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria in BNIP3-mediated cell death was determined in a rat dopaminergic neuronal cell line, Mes 23.5. BNIP3 mutants were constructed to target either ER or mitochondria. Localization of BNIP3 to the ER membrane facilitated release of Ca2+ and subsequently increased uptake of Ca2+ into mitochondria. Excessive accumulation of mitochondrial Ca2+ decreased mitochondrial membrane potential (ΔΨ m), resulting in execution of a caspase-independent cell death. Reduction of ER Ca2+ induced by ER-targeted BNIP3 and the subsequent cell death was blocked by the antiapoptotic protein, Bcl-2. On the other hand, mitochondria-targeted BNIP3 initiated apoptosis by a Ca2+-independent mechanism by inducing mitochondrial pore transition and dissipation of ΔΨ m. The disruption of ΔΨ m and cell death was not blocked by Bcl-2 overexpression. These findings show that BNIP3 undergoes a dual subcellular localization and initiates different cell death signaling events in the ER and mitochondria. Bcl-2 counters the BNIP3-initiated mobilization of ER Ca2+ depletion to reduce the level of apoptosis.
- Subjects
CELL death; ENDOPLASMIC reticulum; MITOCHONDRIA; PROTEINS; APOPTOSIS
- Publication
FASEB Journal, 2009, Vol 23, Issue 10, p3405
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-124354