Summary
B-cell lymphoma 2 (BCL-2) family proteins gather at the biologic cross-roads of renal
cell survival: the outer mitochondrial membrane. Despite shared sequence and structural
features, members of this conserved protein family constantly antagonize each other
in a life-and-death battle. BCL-2 members innocently reside within renal cells until
activated or de-activated by physiologic stresses caused by common nephrotoxins, transient
ischemia, or acute glomerulonephritis. Recent experimental data not only illuminate
the intricate mechanisms of apoptosis, the most familiar form of BCL-2–mediated cell
death, but emphasizes their newfound roles in necrosis, necroptosis, membrane pore
transition regulated necrosis, and other forms of acute cell demise. A major paradigm
shift in non–cell death roles of the BCL-2 family has occurred. BCL-2 proteins also
regulate critical daily renal cell housekeeping functions including cell metabolism,
autophagy (an effective means for recycling cell components), mitochondrial morphology
(organelle fission and fusion), as well as mitochondrial biogenesis. This article
considers new concepts in the biochemical and structural regulation of BCL-2 proteins
that contribute to membrane pore permeabilization, a universal feature of cell death.
Despite these advances, persistent BCL-2 family mysteries continue to challenge cell
biologists. Given their interface with many intracellular functions, it is likely
that BCL-2 proteins determine cell viability under many pathologic circumstances relevant
to the nephrologist and, as a consequence, represent an ideal therapeutic target.
Keywords
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Article info
Footnotes
☆☆Financial support: The basic science described in this article was supported by a research grant from the National Institutes of Health–National Institute of Diabetes and Digestive and Kidney Diseases (53387 to S.B.).
☆Conflicts of interest statement: none.
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