Most cited article - PubMed ID 19777870
Tissue specific sensitivity of mitochondrial permeability transition pore to Ca2+ ions
The mitochondrial permeability transition pore (MPTP) is a calcium-dependent, ion non-selective membrane pore with a wide range of functions. Although the MPTP has been studied for more than 50 years, its molecular structure remains unclear. Short-term (reversible) opening of the MPTP protects cells from oxidative damage and enables the efflux of Ca2+ ions from the mitochondrial matrix and cell signaling. However, long-term (irreversible) opening induces processes leading to cell death. Ca2+ ions, reactive oxygen species, and changes in mitochondrial membrane potential regulate pore opening. The sensitivity of the pore to Ca2+ ions changes as an organism ages, and MPTP opening plays a key role in the pathogenesis of many diseases. Most studies of the MPTP have focused on elucidating its molecular structure. However, understanding the mechanisms that will inhibit the MPTP may improve the treatment of diseases associated with its opening. To evaluate the functional state of the MPTP and its inhibitors, it is therefore necessary to use appropriate methods that provide reproducible results across laboratories. This review summarizes our current knowledge of the function and regulation of the MPTP. The latter part of the review introduces two optimized methods for evaluating the functional state of the pore under standardized conditions.
- Keywords
- calcium retention capacity, calcium signaling, calcium-induced swelling, mitochondria, mitochondrial permeability transition, mitochondrial permeability transition pore,
- MeSH
- Cell Death MeSH
- Mitochondria metabolism MeSH
- Mitochondrial Permeability Transition Pore * metabolism MeSH
- Mitochondrial Membrane Transport Proteins * metabolism MeSH
- Calcium metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Mitochondrial Permeability Transition Pore * MeSH
- Mitochondrial Membrane Transport Proteins * MeSH
- Calcium MeSH
Values of the calcium retention capacity (CRC) of rat liver mitochondria are highly dependent on the experimental conditions used. When increasing amounts of added calcium chloride are used (1.25-10 nmol), the values of the CRC increase 3-fold. When calcium is added in 75 s intervals, the CRC values increase by 30 % compared with 150 s interval additions. CRC values are not dependent on the calcium/protein ratio in the measured sample in our experimental design. We also show that a more detailed evaluation of the fluorescence curves can provide new information about mitochondrial permeability transition pore opening after calcium is added.
- MeSH
- Biological Transport MeSH
- Mitochondria, Liver metabolism MeSH
- Liver metabolism MeSH
- Rats MeSH
- Mitochondrial Membranes metabolism MeSH
- Permeability MeSH
- Mitochondrial Permeability Transition Pore metabolism MeSH
- Mitochondrial Membrane Transport Proteins metabolism MeSH
- Calcium metabolism MeSH
- Research Design MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Names of Substances
- Mitochondrial Permeability Transition Pore MeSH
- Mitochondrial Membrane Transport Proteins MeSH
- Calcium MeSH