Abstract
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-x(L) can inhibit these changes in cells treated with apoptotic stimuli. In addition, Bcl-x(L)-expressing cells adapt to growth factor withdrawal or staurosporine treatment by maintaining a decreased mitochondrial membrane potential. Bcl-x(L) expression also prevents mitochondrial swelling in response to agents that inhibit oxidative phosphorylation. These data suggest that Bcl-x(L) promotes cell survival by regulating the electrical and osmotic homeostasis of mitochondria.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 627-637 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 91 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 28 1997 |
Funding
We thank members of the laboratory and B. Glick for thoughtful discussions and review of the manuscript. This work was supported in part by grants from the National Institutes of Health.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology