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<p>The mitochondrial membrane potential (ΔΨ<sub>m</sub>) drives oxidative phosphorylation and alterations contribute to cardiac pathologies, but real-time assessment of ΔΨ<sub>m</sub> has not been possible. Here we describe noninvasive measurements using mitochondrial heme <i>b</i><sub>L</sub> and <i>b</i><sub>H</sub> absorbances, which rapidly respond to ΔΨ<sub>m</sub>. Multi-wavelength absorbance spectroscopy enabled their continuous monitoring in isolated mitochondria and the perfused heart. Calibration of heme <i>b</i> absorbance in isolated mitochondria revealed that reduced heme <i>b</i><sub>L</sub> relative to total reduced heme <i>b</i> (f<i>b</i><sub>L</sub> = <i>b</i><sub>L</sub>/(<i>b</i><sub>L</sub> + <i>b</i><sub>H</sub>)) exhibits a sigmoidal relationship with ΔΨ<sub>m</sub>. Extrapolating this relationship to the heart enabled estimation of ΔΨ<sub>m</sub> as 166 ± 18 mV (<i>n</i> = 25, mean ± s.d.). We used this approach to assess how ΔΨ<sub>m</sub> changes during ischemia–reperfusion injury, an unknown limiting the understanding of ischemia–reperfusion injury. In perfused hearts, ΔΨ<sub>m</sub> declined during ischemia and rapidly reestablished upon reperfusion, supported by oxidation of the succinate accumulated during ischemia. These findings expand our understanding of ischemia–reperfusion injury.</p>

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Rapid mitochondrial repolarization upon reperfusion after cardiac ischemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月11日

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  • Abigail V. Giles,
  • Raul Covian,
  • Hiran A. Prag,
  • Nils Burger,
  • Bertrand Lucotte,
  • Chak Shun Yu,
  • Junhui Sun,
  • Elizabeth Murphy,
  • Thomas Krieg,
  • Michael P. Murphy,
  • Robert S. Balaban

摘要

The mitochondrial membrane potential (ΔΨm) drives oxidative phosphorylation and alterations contribute to cardiac pathologies, but real-time assessment of ΔΨm has not been possible. Here we describe noninvasive measurements using mitochondrial heme bL and bH absorbances, which rapidly respond to ΔΨm. Multi-wavelength absorbance spectroscopy enabled their continuous monitoring in isolated mitochondria and the perfused heart. Calibration of heme b absorbance in isolated mitochondria revealed that reduced heme bL relative to total reduced heme b (fbL = bL/(bL + bH)) exhibits a sigmoidal relationship with ΔΨm. Extrapolating this relationship to the heart enabled estimation of ΔΨm as 166 ± 18 mV (n = 25, mean ± s.d.). We used this approach to assess how ΔΨm changes during ischemia–reperfusion injury, an unknown limiting the understanding of ischemia–reperfusion injury. In perfused hearts, ΔΨm declined during ischemia and rapidly reestablished upon reperfusion, supported by oxidation of the succinate accumulated during ischemia. These findings expand our understanding of ischemia–reperfusion injury.