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Thapsigargin directly induces the mitochondrial permeability transition.
1The UCLA Cardiovascular Research Laboratory, Department of Medicine (Cardiology), UCLA School of Medicine, Los Angeles, CA 90095-1760, USA.
European Journal of Biochemistry
|September 22, 1999
Summary
Thapsigargin (TG) triggers mitochondrial permeability transition (MPT) in liver and heart mitochondria. This process, crucial for cell death, involves calcium release from mitochondrial sites and is inhibited by cyclosporin A.
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial Research
Background:
- High concentrations of thapsigargin (TG) are utilized to investigate necrotic cell death.
- Necrotic cell death involves the rapid induction of mitochondrial permeability transition (MPT).
Purpose of the Study:
- To investigate the effects of thapsigargin (TG) on mitochondrial permeability transition (MPT).
- To elucidate the mechanism by which TG induces MPT in isolated liver and heart mitochondria.
Main Methods:
- Utilized a matrix swelling assay to assess MPT.
- Employed a novel enzymatic method to determine inner membrane permeability to citrate synthase substrates.
- Investigated the role of extramitochondrial calcium and cyclosporin A inhibition.
Main Results:
- Thapsigargin (TG) induced MPT in a concentration-dependent manner.
- The TG-induced MPT was independent of extramitochondrial calcium concentrations.
- Cyclosporin A effectively inhibited the MPT induced by TG.
- Evidence suggests TG causes MPT via calcium release from mitochondrial matrix binding sites.
Conclusions:
- Thapsigargin (TG) directly induces mitochondrial permeability transition (MPT) in isolated mitochondria.
- The mechanism involves calcium release from mitochondrial matrix binding sites.
- The MPT-inducing effect of TG may contribute to its pro-necrotic and pro-apoptotic roles in cells.