SOD2 overexpression: Enhanced mitochondrial tolerance but absence of effect on UCP activity

José P. Silva, Irina G. Shabalina, Eric Dufour, Natasa Petrovic, Emma C. Backlund, Kjell Hultenby, Rolf Wibom, Jan Nedergaard, Barbara Cannon, Nils Göran Larsson

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


We have created P1 artificial chromosome transgenic mice expressing the human mitochondrial superoxide dismutase 2 (SOD2) and thus generated mice with a physiologically controlled augmentation of SOD2 expression leading to increased SOD2 enzyme activities and lowered superoxide levels. In the transgenic mice, effects on mitochondrial function such as enhanced oxidative capacity and greater resistance against inducers of mitochondrial permeability were observed. Superoxide in the mitochondrial matrix has been proposed to activate uncoupling proteins (UCPs), thus providing a feedback mechanism that will lower respiratory chain superoxide production by increasing a proton leak across the inner mitochondrial membrane. However, UCP1 and UCP3 activities and mitochondrial ATP production rates were not altered in isolated mitochondria from SOD2 transgenic mice, despite lowered superoxide levels. Globally, the transgenic mice displayed normal resting metabolic rates, indicating an absence of effect on any UCP activities, and normal oxygen consumption responses after norepinephrine injection. These results strongly suggest that endogenously generated matrix superoxide does not regulate UCP activity and in vivo energy expenditure.

Original languageEnglish (US)
Pages (from-to)4061-4070
Number of pages10
JournalEMBO Journal
Issue number23
StatePublished - Dec 7 2005
Externally publishedYes


  • Energy expenditure
  • Mitochondria
  • Superoxide
  • Transgenic mice
  • Uncoupling protein

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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