Difference between revisions of "Schirris 2015 Cell Metab"
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{{Publication | {{Publication | ||
|title=Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG (2015) Statin-induced myopathy is associated with mitochondrial complex III inhibition. Cell Metab 22:399-407. | |title=Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG (2015) Statin-induced myopathy is associated with mitochondrial complex III inhibition. Cell Metab 22:399-407. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/26331605 PMID: 26331605] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/26331605 PMID: 26331605] | ||
|authors=Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG | |authors=Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG | ||
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|journal=Cell Metab | |journal=Cell Metab | ||
|abstract=Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscle tissue of patients suffering from statin-induced myopathies, in which CIII enzyme activity was reduced by 18%. Respiratory inhibition in C2C12 myoblasts could be attenuated by convergent electron flow into CIII, restoring respiration up to 89% of control. In conclusion, CIII inhibition was identified as a potential off-target mechanism associated with statin-induced myopathies. | |abstract=Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscle tissue of patients suffering from statin-induced myopathies, in which CIII enzyme activity was reduced by 18%. Respiratory inhibition in C2C12 myoblasts could be attenuated by convergent electron flow into CIII, restoring respiration up to 89% of control. In conclusion, CIII inhibition was identified as a potential off-target mechanism associated with statin-induced myopathies. | ||
|mipnetlab=NL Nijmegen Koopman WJ | |keywords=C2C12 myoblasts | ||
|mipnetlab=NL Nijmegen Koopman WJ, NL Nijmegen Brandt U, NL Nijmegen Rodenburg R | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Patients, Pharmacology;toxicology | ||
|diseases=Myopathy | |||
|organism=Human, Mouse | |organism=Human, Mouse | ||
|tissues=Skeletal muscle | |tissues=Skeletal muscle, Other cell lines | ||
|preparations=Permeabilized cells | |preparations=Permeabilized cells | ||
|enzymes=Complex III, Complex V;ATP synthase | |enzymes=Complex III, Complex V;ATP synthase | ||
|couplingstates=ROUTINE, OXPHOS, ET | |||
|couplingstates=ROUTINE, OXPHOS, | |pathways=N, S, Gp, CIV, NS, ROX | ||
| | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 14:36, 27 March 2018
| Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG (2015) Statin-induced myopathy is associated with mitochondrial complex III inhibition. Cell Metab 22:399-407. |
Schirris TJ, Renkema GH, Ritschel T, Voermans NC, Bilos A, van Engelen BG, Brandt U, Koopman WJ, Beyrath JD, Rodenburg RJ, Willems PH, Smeitink JA, Russel FG (2015) Cell Metab
Abstract: Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscle tissue of patients suffering from statin-induced myopathies, in which CIII enzyme activity was reduced by 18%. Respiratory inhibition in C2C12 myoblasts could be attenuated by convergent electron flow into CIII, restoring respiration up to 89% of control. In conclusion, CIII inhibition was identified as a potential off-target mechanism associated with statin-induced myopathies. • Keywords: C2C12 myoblasts
• O2k-Network Lab: NL Nijmegen Koopman WJ, NL Nijmegen Brandt U, NL Nijmegen Rodenburg R
Labels: MiParea: Respiration, Patients, Pharmacology;toxicology
Pathology: Myopathy
Organism: Human, Mouse Tissue;cell: Skeletal muscle, Other cell lines Preparation: Permeabilized cells Enzyme: Complex III, Complex V;ATP synthase
Coupling state: ROUTINE, OXPHOS, ET Pathway: N, S, Gp, CIV, NS, ROX HRR: Oxygraph-2k
