Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin

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Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
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Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation

Published on: January 10, 2025

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Xiuling Shang1, Jun Li1, Rongguo Yu2

  • 1Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou, 350001, Fujian, China.

Journal of Molecular Histology
|January 4, 2019
PubMed

Insights

Septic cardiomyopathy involves mitochondrial stress. This study reveals the Mst1/Drp1 pathway drives mitochondrial fission, leading to heart cell death and F-actin degradation, offering new therapeutic targets.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Biology
  • Cellular Stress Response

Background:

  • Sepsis-induced cardiomyopathy is linked to mitochondrial dysfunction.
  • Mitochondrial fission is an early indicator of mitochondrial dysfunction.
  • The precise mechanisms linking sepsis to mitochondrial stress remain unclear.

Purpose of the Study:

  • To investigate the role of mitochondrial fission in LPS-induced septic cardiomyopathy.
  • To elucidate the regulatory mechanism of mitochondrial fission, focusing on Mst1 and F-actin.
  • To identify potential therapeutic targets for sepsis-related myocardial injury.

Main Methods:

  • Assessed Mst1 expression in LPS-treated heart tissue.
  • Investigated the effect of Mst1 on cardiomyocyte death and mitochondrial stress.
  • Examined the role of the Mst1/Drp1 pathway in initiating mitochondrial fission.
  • Evaluated the impact of mitochondrial fission inhibition on cardiac function.
  • Analyzed F-actin degradation as a downstream event of mitochondrial fission.

Main Results:

  • LPS treatment rapidly upregulated Mst1 expression in the heart.
  • Increased Mst1 promoted cardiomyocyte death via mitochondrial stress.
  • Mst1 upregulation led to Drp1 activation and subsequent mitochondrial fission.
  • Excessive mitochondrial fission resulted in oxidative injury, reduced membrane potential, energy dysfunction, and apoptosis.
  • Inhibition of mitochondrial fission preserved mitochondrial function and cardiomyocyte survival.
  • F-actin degradation was identified as a downstream consequence of mitochondrial fission.
  • Stabilizing F-actin reduced fission-mediated cardiomyocyte death.

Conclusions:

  • The Mst1/Drp1/mitochondrial fission/F-actin axis is a novel pathway mediating LPS-induced septic cardiomyopathy.
  • This pathway induces mitochondrial stress and cardiomyocyte death.
  • Mst1, mitochondrial fission, and F-actin stabilization are potential therapeutic targets for sepsis-related myocardial injury.
Keywords:
F-actinLPSMitochondrial fissionMst1Septic cardiomyopathy

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