Mitochondrial metabolism and dynamics in the development of diabetic kidney disease

Over 40% of individuals with diabetes are affected by diabetic kidney disease (DKD), a major cause of end-stage renal disease worldwide.

• Mitochondrial dysfunction is implicated as the central mechanism in the progression of DKD.
• Hyperglycemia-induced metabolic stress affects mitochondrial functions, resulting in increased reactive oxygen species and damaged mitochondrial DNA.
• Alterations in mitochondrial fission, fusion, and quality control processes occur early in DKD and impact various kidney cell types.
• Key molecular regulators, such as those involved in mitophagy and mitochondrial biogenesis, are identified as potential therapeutic targets.
• Current therapeutic options targeting mitochondrial dysfunction include sodium-glucose cotransporter 2 (SGLT2) inhibitors and mitochondria-targeted antioxidants, with SGLT2 inhibitors showing the most robust evidence from randomized controlled trials.

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