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Updated: Feb 11, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

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Glycogen synthase kinase-3β opens mitochondrial permeability transition pore through mitochondrial hexokinase II

Takamitsu Tanaka1, Masao Saotome2, Hideki Katoh1

  • 1Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.

The Journal of Physiological Sciences : JPS
|April 20, 2018
PubMed

Insights

Glycogen synthase kinase-3β (GSK3β) inactivation protects the heart by regulating mitochondrial hexokinase II (mitoHK-II) binding and preventing mitochondrial permeability transition pore (mPTP) opening during ischemia/reperfusion injury.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Glycogen synthase kinase-3β (GSK3β) inactivation is recognized for its cardiac protective effects.
  • The exact mechanisms underlying GSK3β-mediated protection against ischemia/reperfusion (I/R) injury are not fully understood.

Purpose of the Study:

  • To investigate the link between GSK3β-inactivation, mitochondrial hexokinase II (mitoHK-II) dissociation, and mitochondrial permeability transition pore (mPTP) opening.
  • To elucidate the role of mitoHK-II binding and activity in GSK3β-regulated mPTP opening.

Main Methods:

  • Langendorff-perfused heart model to assess cardiac function and mitoHK-II binding post-I/R.
  • Permeabilized myocyte experiments to evaluate mitochondrial membrane potential, mPTP opening, and mitoHK-II binding.
  • Pharmacological manipulation of GSK3β, mitoHK-II binding, and mitoHK-II activity.

Main Results:

  • GSK3β inactivation improved cardiac function and maintained mitoHK-II binding after I/R.
  • GSK3β activation led to mitochondrial depolarization, increased mPTP opening, and decreased mitoHK-II binding.
  • GSK3β-mediated mPTP opening was modulated by mitoHK-II binding status and activity.

Conclusions:

  • GSK3β-mediated mPTP opening appears to contribute to I/R injury.
  • MitoHK-II binding and enzymatic activity are key regulators of GSK3β-induced mPTP opening, offering potential therapeutic targets.
Keywords:
Glycogen synthase kinase-3βIschemia–reperfusionMitochondrial hexokinase IIMitochondrial permeability transition pore

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