Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes

A. Makino, B. T. Scott, W. H. Dillmann

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Aims/hypothesis: Mitochondria frequently change their shapes by fusion and fission and these morphological dynamics play important roles in mitochondrial function and development as well as programmed cell death. The goal of this study is to investigate whether: (1) mitochondria in mouse coronary endothelial cells (MCECs) isolated from diabetic mice exhibit increased fragmentation; and (2) chronic treatment with a superoxide anion (O2 - ) scavenger has a beneficial effect on mitochondrial fragmentation in MCECs. Methods: MCECs were freshly isolated and lysed for protein measurement, or cultured to determine mitochondrial morphology and O2 - production. For the ex vivo hyperglycaemia experiments, human coronary endothelial cells were used. Results: Elongated mitochondrial tubules were observed in MCECs isolated from control mice, whereas mitochondria in MCECs from diabetic mice exhibited augmented fragmentation. The level of optic atrophy 1 (OPA1) protein, which leads to mitochondrial fusion, was significantly decreased, while dynamin-related protein 1 (DRP1), which leads to mitochondrial fission, was significantly increased in MCECs from diabetic mice. Diabetic MCECs exhibited significantly higher O2 - concentrations in cytosol and mitochondria than control MCECs. Administration of the O2 - scavenger TEMPOL to diabetic mice for 4 weeks led to a significant decrease in mitochondrial fragmentation without altering the levels of OPA1 and DRP1 proteins in MCECs. High-glucose treatment for 24 h significantly induced mitochondrial fragmentation, which was restored by TEMPOL treatment. In addition, excess O2 - production, either in cytosol or in mitochondria, significantly increased mitochondrial fragmentation. Conclusions/interpretation: These data suggest that lowering the O2 - concentration can restore the morphological change in mitochondria and may help improve mitochondrial function in diabetic MCECs.

Original languageEnglish (US)
Pages (from-to)1783-1794
Number of pages12
JournalDiabetologia
Volume53
Issue number8
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Keywords

  • DRP1
  • Endothelium
  • Fission
  • Fusion
  • Mitochondrial dynamics
  • O
  • OPA1
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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