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Mitochondrial STING Governs Glycolytic Reprogramming in Diabetic Cardiomyopathy.

Shiwu Zhang1, Dechao Zhao2, Mengyi Wang1,3

  • 1State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Depart ment of Pathophysiology, School of Basic Medical Sciences, Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, The Key Laboratory of Myocardial Ischemia, Ministry of Education (S.Z., M.W., F.Y., Z.T., H.D., F.L., X.Z., H.C., J.K., J.T., B.Y., W.Z.), Harbin Medical University, China.

Circulation Research
|July 2, 2026
PubMed
Summary
This summary is machine-generated.

STING protein dysregulation contributes to diabetic cardiomyopathy by impairing mitochondrial function and altering metabolism. Restoring hydrogen sulfide levels or targeting STING palmitoylation offers a potential therapeutic approach for this condition.

Keywords:
diabetic cardiomyopathiesinflammationmetabolismmitochon driastreptozotocin

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Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Metabolic Disease

Background:

  • Diabetic cardiomyopathy involves mitochondrial dysfunction and inflammation.
  • The role of STING (stimulator of interferon genes) in diabetic cardiac metabolic regulation is unclear.

Purpose of the Study:

  • Investigate STING's function in diabetic cardiac remodeling.
  • Elucidate STING's impact on mitochondrial dynamics and metabolism in diabetes.

Main Methods:

  • Utilized single-cell RNA sequencing, echocardiography, and electron microscopy in diabetic mouse models.
  • Assessed mitochondrial respiration and glycolytic flux using Seahorse analysis.
  • Examined STING posttranslational modifications and its interaction with ENO1 and TOM40.

Main Results:

  • STING translocates to mitochondria, disrupting homeostasis and protein import.
  • Mitochondrial STING enhances ENO1 activity, increasing glycolytic flux and lactate.
  • Reduced hydrogen sulfide levels promote STING palmitoylation and mitochondrial localization.

Conclusions:

  • STING acts as an immunometabolic regulator in diabetic cardiomyopathy.
  • STING links mitochondrial dysfunction to metabolic imbalance.
  • Targeting STING S-sulfhydration or palmitoylation presents a therapeutic avenue.