Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease

Melinda T. Coughlan, Kumar Sharma

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations


The paradigm that high glucose drives overproduction of superoxide from mitochondria as a unifying theory to explain end organ damage in diabetes complications has been tightly held for more than a decade. With the recent development of techniques and probes to measure the production of distinct reactive oxygen species (ROS) in vivo, this widely held dogma is now being challenged with the emerging view that specific ROS moieties are essential for the function of specific intracellular signaling pathways and represent normal mitochondrial function. This review will provide a balanced overview of the dual nature of ROS, detailing current evidence for ROS overproduction in diabetic kidney disease, with a focus on cell types and sources of ROS. The technical aspects of measurement of mitochondrial ROS, both in isolated mitochondria and emerging in vivo methods will be discussed. The counterargument, that mitochondrial ROS production is reduced in diabetic complications, is consistent with a growing recognition that stimulation of mitochondrial biogenesis and oxidative phosphorylation activity reduces inflammation and fibrosis. It is clear that there is an urgent need to fully characterize ROS production paying particular attention to spatiotemporal aspects and to factor in the relevance of ROS in the regulation of cellular signaling in the pathogenesis of diabetic kidney disease. With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens.

Original languageEnglish (US)
Pages (from-to)272-279
Number of pages8
JournalKidney international
Issue number2
StatePublished - Aug 1 2016
Externally publishedYes


  • diabetic nephropathy
  • mitochondria
  • oxidative stress

ASJC Scopus subject areas

  • Nephrology


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