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

• Author(s) / Creator(s)

  • Chan, Catherine B.
  • Bikopoulos, George
  • Koshkin, Vasilij
  • Wheeler, Michael B.

• 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.

• Date created

  2004

• Subjects / Keywords

  • Metabolism
  • Bioenergetics

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R3988315J

• License

  © 2004 by The American Society for Biochemistry and Molecular Biology, Inc.