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dc.contributor.authorPohl, Sebastian
dc.contributor.authorAgostino, Mark
dc.contributor.authorDharmarajan, Arunasalam
dc.contributor.authorPervaiz, Shazib
dc.identifier.citationPohl, S. and Agostino, M. and Dharmarajan, A. and Pervaiz, S. 2018. Cross talk between cellular redox state and the antiapoptotic protein Bcl-2. Antioxidants & Redox Signaling. 29 (13): pp. 1215-1236.

SIGNIFICANCE B cell lymphoma-2 (Bcl-2) is the prototypical anti-apoptotic member of the Bcl-2 family that comprises proteins with contrasting effects on cell fate. Identified as a consequence chromosomal translocation (t 14:18) in human lymphoma, subsequent studies have revealed mutations and/or copy number alterations, as well as post-translational modifications, of Bcl-2 in a variety of cancers. The canonical function of Bcl-2 is linked to its ability to inhibit mitochondrial membrane permeabilization, regulating apoptosome assembly and activation by blocking cytosolic translocation of death amplification factors. RECENT ADVANCES Aside from maintaining mitochondrial integrity, a novel facet of Bcl-2 biology involves crosstalk with cellular redox state. Bcl-2 overexpression modulates mitochondrial redox metabolism to create a 'pro-oxidant' milieu, conducive for cell survival. Under oxidative stress, Bcl-2 functions as a redox sink to prevent excessive build-up of reactive oxygen species, inhibiting execution signals. Evidence indicates various redox-dependent transcriptional changes and post-translational modifications with different functional outcomes. CRITICAL ISSUES Understanding the complex interplay between Bcl-2 and the cellular redox milieu from the standpoint of cell fate signaling remains vital for understanding pathological states associated with altered redox metabolism and/or aberrant Bcl-2 expression. FUTURE DIRECTIONS Small molecule inhibitors of Bcl-2 are showing promise in the clinic. The non-canonical activity linked to cellular redox metabolism provides a novel avenue for the design and development of diagnostic and therapeutic strategies against cancers refractory to conventional chemotherapy.

dc.publisherMary Ann Liebert, Inc. Publishers
dc.titleCross talk between cellular redox state and the antiapoptotic protein Bcl-2
dc.typeJournal Article
dcterms.source.titleAntioxidants & Redox Signaling

Final publication is available from Mary Ann Liebert, Inc., publishers at

curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access

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