Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress

Chad A. Galloway, Hakjoo Lee, Souad Nejjar, Bong Sook Jhun, Tianzheng Yu, Wei Hsu, Yisang Yoon

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with the continuous shape change of mitochondria mediated by fission and fusion, as evidenced not only by the hereditary diseases caused by mutations in fission/fusion genes but also by aberrant mitochondrial morphologies associated with numerous pathologic insults. However, how morphological change of mitochondria is linked to their energy-producing activity is poorly understood. In this study, we found that perturbation of mitochondrial fission induces a unique mitochondrial uncoupling phenomenon through a large-scale fluctuation of a mitochondrial inner membrane potential. Furthermore, by genetically controlling mitochondrial fission and thereby inducing mild proton leak in mice, we were able to relieve these mice from oxidative stress in a hyperglycemic model. These findings provide mechanistic insight into how mitochondrial fission participates in regulating mitochondrial activity. In addition, these results suggest a potential application of mitochondrial fission to control mitochondrial reactive oxygen species production and oxidative stress in many human diseases.

Original languageEnglish (US)
Pages (from-to)2093-2104
Number of pages12
JournalDiabetes
Volume61
Issue number8
DOIs
StatePublished - Aug 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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