The characterization of mitochondrial permeability transition (MPT) in clonal pancreatic beta cells: Multiple modes and regulation

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  • Mitochondrial permeability transition (MPT), which contributes substantially to the regulation of normal mitochondrial metabolism, also plays a crucial role in the initiation of cell death. It is known that MPT is regulated in a tissue-specific manner. The importance of MPT in the pancreatic β-cell is heightened by the fact that mitochondrial bioenergetics serve as the main glucose-sensing regulator and energy source for insulin secretion. In the present study, using MIN6 and INS-1 β-cells, we revealed that both Ca2+-phosphate- and oxidant-induced MPT is remarkably different from other tissues. Ca2+-phosphate-induced transition is accompanied by a decline in mitochondrial reactive oxygen species production related to a significant potential dependence of reactive oxygen species formation in β-cell mitochondria. Hydroperoxides, which are indirect MPT co-inducers active in liver and heart mitochondria, are inefficient in β-cell mitochondria, due to the low mitochondrial ability to metabolize them. Direct cross-linking of mitochondrial thiols in pancreatic β-cells induces the opening of a low conductance ion permeability of the mitochondrial membrane instead of the full scale MPT opening typical for liver mitochondria. Low conductance MPT is independent of both endogenous and exogenous Ca2+, suggesting a novel type of nonclassical MPT in β-cells. It results in the conversion of electrical transmembrane potential into ΔpH instead of a decrease in total protonmotive force, thus mitochondrial respiration remains in a controlled state. Both Ca2+- and oxidant-induced MPTs are phosphate-dependent and, through the “phosphate flush” (associated with stimulation of insulin secretion), are expected to participate in the regulation in β-cell glucose-sensing and secretory activity.

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    © 2004 by The American Society for Biochemistry and Molecular Biology, Inc.
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    • Koshkin, V., Bikopoulos, G., Chan, C. B., & Wheeler, M. B. (2004). The characterization of mitochondrial permeability transition (MPT) in clonal pancreatic beta cells: Multiple modes and regulation. Journal of Biological Chemistry, 279(40), 41368-41376.
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