Bcl-2 regulation of mitochondrial energetics.
Recent data suggest that in addition to regulating apoptosis, Bcl-2 (an anti-apoptotic protein overexpressed in B-cell lymphoma) and Bcl-2 family members also regulate mitochondrial and cell physiology. t-Bid, a Bcl-2 family member, has been shown to modulate reorganization of mitochondrial cristae. Bcl-2 appears to regulate voltage-dependent anion channel permeability, which has important consequences for mitochondrial transport of adenine nucleotides, Ca(2+), and other metabolites. BAD, a pro-apoptotic Bcl-2 family member, is required for the binding of glucokinase to a mitochondrial complex, and BAD null mice have altered glucose homeostasis. It has been suggested that Bcl-2 family members may regulate important mitochondrial/cell functions and serve as sentinels to detect abnormalities in these pathways and, when the abnormalities are severe enough, to initiate or facilitate cell death. Understanding the physiologic processes controlled by Bcl-2 will be important in understanding cell regulation, and it may also provide new insights into the regulation of apoptosis.
Murphy
Elizabeth
E
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. murphy1@niehs.nih.gov
Imahashi
Ken-ichi
K
Steenbergen
Charles
C
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002452:Cell Count; D002462:Cell Membrane / Q000502:physiology; D004579:Electron Transport / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate