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Circulating cell-free mitochondrial DNA in diabetes mellitus: Current insights and unexplored frontiers

Mohammadreza Akbari1, Fatemeh Masjedi1, Mohammad Nekooeian1

  • 1Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Journal of Diabetes Investigation
|June 12, 2025
PubMed

Insights

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is increasingly linked to diabetes and its complications. This review explores ccf-mtDNA

Area of Science:

  • Mitochondrial Biology
  • Immunology
  • Endocrinology

Background:

  • Circulating cell-free mitochondrial DNA (ccf-mtDNA) is released into plasma via mitochondrial dysfunction, cell death, and NETosis.
  • Elevated levels of ccf-mtDNA are observed in diabetes and its complications.
  • ccf-mtDNA can activate immune pathways due to its similarity to pathogenic DNA, contributing to inflammation.

Purpose of the Study:

  • To review current research on the role of ccf-mtDNA in diabetes pathophysiology.
  • To explore ccf-mtDNA's potential as a diagnostic, prognostic, and therapeutic target in diabetes.
  • To identify research gaps concerning ccf-mtDNA in various diabetes types.

Main Methods:

  • Literature review synthesizing existing studies on ccf-mtDNA and diabetes.
  • Analysis of immunological pathways linking ccf-mtDNA and diabetes.
  • Focus on type 2 diabetes, with consideration for other forms like type 1 and gestational diabetes.

Main Results:

  • Significant overlap exists between immunological pathways activated by ccf-mtDNA and those implicated in diabetes.
  • ccf-mtDNA is proposed to play a key role in the pathophysiology of diabetes and its complications.
  • Research is predominantly focused on type 2 diabetes, with limited data on type 1 diabetes.

Conclusions:

  • ccf-mtDNA emerges as a significant factor in diabetes pathogenesis and complications.
  • ccf-mtDNA holds potential as a biomarker and therapeutic target for diabetes.
  • Further research is needed, particularly on ccf-mtDNA's role in type 1 and gestational diabetes.
Keywords:
Cell‐free nucleic acidsDiabetes mellitusMitochondrial DNA

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