Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart

Ossama M. Lashin, Pamela A. Szweda, Luke I. Szweda, Andrea M P Romani

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Several lines of research suggest that mitochondria play a role in the etiopathogenesis of diabetic cardiomyopathy, although the mechanisms involved are still debated. In the present study, we report that State 3 oxygen consumption decreases by ∼35% with glutamate and by ∼30% with succinate in mitochondria from diabetic rat hearts compared to controls. In these mitochondria the enzymatic activities of complex I and complex II are also decreased to a comparable extent. Western blot analysis of mitochondrial protein pattern using antibodies recognizing proteins modified by the lipid peroxidation product 4-hydroxynonenal indicates the FAD-containing subunit of succinate dehydrogenase as one of the targets of this highly reactive aldehyde. In rats diabetic for 6 or 12 weeks, insulin supplementation for 2 weeks decreases the level of protein modified by 4-hydroxynonenal and restores mitochondrial respiration and enzyme activity to control level. Taken together, these results: (1) indicate that 4-hydroxynonenal is endogenously produced within diabetic mitochondria and forms an adduct with selective mitochondrial proteins, (2) identify one of these proteins as a subunit of succinate dehydrogenase, and (3) provide strong evidence that insulin treatment can reverse and ameliorate free radical damage and mitochondrial function under diabetic conditions.

Original languageEnglish (US)
Pages (from-to)886-896
Number of pages11
JournalFree Radical Biology and Medicine
Issue number5
StatePublished - Mar 1 2006


  • Free radicals
  • HNE
  • Mitochondria
  • Streptozotocin
  • Succinate dehydrogenase
  • Type I diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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