Mitochondrial complex III activity: from invasive muscle biopsies to patient-friendly buccal swab analysis

线粒体复合物 III 活性:从侵入性肌肉活检到患者友好的口腔拭子分析

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作者:Tim Somers, Neeltje A E Allard, Sailay Siddiqi, Margit C M Janssen, Maria T E Hopman, Wim J Morshuis, Frans G M Russel, Silvie Timmers #, Tom J J Schirris #

Abstract

Drug-induced mitochondrial dysfunction is a common adverse effect, particularly in case of statins-the most prescribed drugs worldwide. These drugs have been shown to inhibit complex III (CIII) of the mitochondrial oxidative phosphorylation process, which is related to muscle pain. As muscle pain is the most common complaint of statin users, it is crucial to distinguish it from other causes of myalgia to prevent unnecessary cessation of drug therapy. However, diagnosing CIII inhibition currently requires muscle biopsies, which are invasive and not practical for routine testing. Less invasive alternatives for measurement of mitochondrial complex activities are only available yet for complex I and IV. Here, we describe a non-invasive spectrophotometric method to determine CIII catalytic activities using buccal swabs, which we validated in a cohort of statin and non-statin users. Our data indicate that CIII can be reliably measured in buccal swabs, as evidenced by reproducible results above the detection limit. Further validation on a large-scale clinical setting is recommended.

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