Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress.
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.
Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Chad A
CA
Galloway
Hakjoo
H
Lee
Souad
S
Nejjar
Bong Sook
BS
Jhun
Tianzheng
T
Yu
Wei
W
Hsu
Yisang
Y
Yoon
D000818:Animals; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D014475:Uncoupling Agents / Q000494:pharmacology
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D014475:Uncoupling Agents; C486391:Dnm1l protein, mouse; D034281:Dynamins