We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis.
- Authors
Matsuyama, Shigemi; Llopis, Juan; Deveraux, Quinn L.; Tsien, Roger Y.; Reed, John C.
- Abstract
Mitochondria trigger apoptosis by releasing caspase activators, including cytochrome c (cytC). Here we show, using a pH-sensitive green fluorescent protein (GFP), that mitochondria-dependent apoptotic stimuli (such as Bax, staurosporine and ultraviolet irradiation) induce rapid, Bcl-2-inhibitable mitochondrial alkalinization and cytosol acidification, followed by cytC release, caspase activation and mitochondrial swelling and depolarization. These events are not induced by mitochondria-independent apoptotic stimuli, such as Fas. Activation of cytosolic caspases by cytC in vitro is minimal at neutral pH, but maximal at acidic pH, indicating that mitochondria-induced acidification of the cytosol may be important for caspase activation; this finding is supported by results obtained from cells using protonophores. Cytosol acidification and cytC release are suppressed by oligomycin, a F[sub 0]F[sub 1]-ATPase/H[sup +]-pump inhibitor, but not by caspase inhibitors. Ectopic expression of Bax in wild-type, but not F[sub 0]F[sub 1]/H[sup +]-pump-deficient, yeast cells similarly results in mitochondrial matrix alkalinization, cytosol acidification and cell death. These findings indicate that mitochondria-mediated alteration of intracellular pH may be an early event that regulates caspase activation in the mitochondrial pathway for apoptosis.
- Subjects
MITOCHONDRIA; APOPTOSIS; CYTOSOL
- Publication
Nature Cell Biology, 2000, Vol 2, Issue 6, p318
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/35014006