RRC ID 68646
Author Lee S, Tak E, Lee J, Rashid MA, Murphy MP, Ha J, Kim SS.
Title Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation.
Journal Cell Res
Abstract Mitochondrial reactive oxygen species (mROS) have been considered detrimental to cells. However, their physiological roles as signaling mediators have not been thoroughly explored. Here, we investigated whether mROS generated from mitochondrial electron transport chain (mETC) complex I stimulated muscle differentiation. Our results showed that the quantity of mROS was increased and that manganese superoxide dismutase (MnSOD) was induced via NF-κB activation during muscle differentiation. Mitochondria-targeted antioxidants (MitoQ and MitoTEMPOL) and mitochondria-targeted catalase decreased mROS quantity and suppressed muscle differentiation without affecting the amount of ATP. Mitochondrial alterations, including the induction of mitochondrial transcription factor A and an increase in the number and size of mitochondria, and functional activations were observed during muscle differentiation. In particular, increased expression levels of mETC complex I subunits and a higher activity of complex I than other complexes were observed. Rotenone, an inhibitor of mETC complex I, decreased the mitochondrial NADH/NAD(+) ratio and mROS levels during muscle differentiation. The inhibition of complex I using small interfering RNAs and rotenone reduced mROS levels, suppressed muscle differentiation, and depleted ATP levels with a concomitant increase in glycolysis. From these results, we conclude that complex I-derived O(2)·(-), produced through reverse electron transport due to enhanced metabolism and a high activity of complex I, was dismutated into H(2)O(2) by MnSOD induced via NF-κB activation and that the dismutated mH(2)O(2) stimulated muscle differentiation as a signaling messenger.
Volume 21(5)
Pages 817-34
Published 2011-5-1
DOI 10.1038/cr.2011.55
PII cr201155
PMID 21445095
PMC PMC3203677
MeSH Animals Catalase / metabolism Cell Differentiation* DNA-Binding Proteins / metabolism Electron Transport Complex I / metabolism* Energy Metabolism Gene Knockdown Techniques High Mobility Group Proteins / metabolism Hydrogen Peroxide / metabolism* Mice Mitochondria / enzymology Mitochondria / metabolism* Mitochondria / ultrastructure Muscle Development Muscles / cytology* Muscles / enzymology Muscles / ultrastructure NF-kappa B / metabolism Protein Subunits / metabolism Rats Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Superoxides / metabolism Transcription, Genetic
IF 20.507
Human and Animal Cells P19CL6