Integrative Insights Into Mitochondrial Dysfunction and Organelle Crosstalk in Diabetic Kidney Disease

Mar 21, 2026FASEB journal : official publication of the Federation of American Societies for Experimental Biology

How Mitochondrial Problems and Cell Structure Interactions Are Linked to Kidney Disease in Diabetes

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Abstract

Mitochondrial dysfunction is a major driver of diabetic kidney disease (DKD), contributing to glomerular and tubular injury.

  • Early and sustained mitochondrial dysfunction is associated with metabolic changes, oxidative stress, and inflammation in DKD.
  • Four interrelated mitochondrial factors—metabolic reprogramming, altered fission-fusion dynamics, defective mitophagy, and mtDNA release—are linked to DKD progression.
  • Mitochondria-endoplasmic reticulum contacts (MAMs) play a critical role in integrating redox signaling and calcium balance.
  • Preclinical studies suggest that enhancing mitochondrial function may reduce kidney injury.
  • Clinically approved agents, including metformin and SGLT2 inhibitors, show renoprotective effects through mitochondrial pathways.

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