Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria.
Mitochondrial physiology is disrupted in either apoptosis or necrosis. Here, we report that a wide variety of apoptotic and necrotic stimuli induce progressive mitochondrial swelling and outer mitochondrial membrane rupture. Discontinuity of the outer mitochondrial membrane results in cytochrome c redistribution from the intermembrane space to the cytosol followed by subsequent inner mitochondrial membrane depolarization. The mitochondrial membrane protein Bcl-xL can inhibit these changes in cells treated with apoptotic stimuli. In addition, Bcl-xL-expressing cells adapt to growth factor withdrawal or staurosporine treatment by maintaining a decreased mitochondrial membrane potential. Bcl-xL expression also prevents mitochondrial swelling in response to agents that inhibit oxidative phosphorylation. These data suggest that Bcl-xL promotes cell survival by regulating the electrical and osmotic homeostasis of mitochondria.
Vander Heiden
M G
MG
Gwen Knapp Center and Committee on Immunology, Department of Medicine, University of Chicago, Illinois 60637, USA.
Chandel
N S
NS
Williamson
E K
EK
Schumacker
P T
PT
Thompson
C B
CB
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D003574:Cytochrome c Group / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000473:pathology; D019169:Jurkat Cells / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D008564:Membrane Potentials / Q000502:physiology; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D008933:Mitochondrial Swelling; D010085:Oxidative Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014162:Transfection; D051020:bcl-X Protein
D000900:Anti-Bacterial Agents; C494811:BCL2L1 protein, human; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D000968:Antimycin A