The decylTPP mitochondria-targeting moiety lowers electron transport chain supercomplex levels in primary human skin fibroblasts
| Autor: | Elianne P. Bulthuis, Claudia Einer, Felix Distelmaier, Laszlo Groh, Sjenet E. van Emst - de Vries, Els van de Westerlo, Melissa van de Wal, Jori Wagenaars, Richard J. Rodenburg, Jan A.M. Smeitink, Niels P. Riksen, Peter H.G.M. Willems, Merel J.W. Adjobo-Hermans, Hans Zischka, Werner J.H. Koopman |
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| Rok vydání: | 2022 |
| Předmět: |
Electron Transport Complex I
Mitochondrial Diseases Complex I Glycolysis Mitochondrial Targeting Supercomplexes Trolox Decyltpp Mitochondrial targeting Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Fibroblasts Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Biochemistry Mitochondria decylTPP Electron Transport All institutes and research themes of the Radboud University Medical Center Physiology (medical) Human and Animal Physiology Fysiologie van Mens en Dier Humans |
| Zdroj: | Free Radical Biology and Medicine, 188, pp. 434-446 Free Radical Biology and Medicine 188 (2022) Free Radical Biol. Med. 188, 434-446 (2022) Free Radical Biology and Medicine, 188, 434-446 |
| ISSN: | 0891-5849 |
| Popis: | Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP+) cations is a widely applied strategy for mitochondrial targeting. We previously demonstrated that the vitamin E-derived antioxidant Trolox increases the levels of active mitochondrial complex I (CI), the first complex of the electron transport chain (ETC), in primary human skin fibroblasts (PHSFs) of Leigh Syndrome (LS) patients with isolated CI deficiency. Primed by this finding, we here studied the cellular effects of mitochondria-targeted Trolox (MitoE10), mitochondria-targeted ubiquinone (MitoQ10) and their mitochondria-targeting moiety decylTPP (C10-TPP+). Chronic treatment (96 h) with these molecules of PHSFs from a healthy subject and an LS patient with isolated CI deficiency (NDUFS7-V122 M mutation) did not greatly affect cell number. Unexpectedly, this treatment reduced CI levels/activity, lowered the amount of ETC supercomplexes, inhibited mitochondrial oxygen consumption, increased extracellular acidification, altered mitochondrial morphology and stimulated hydroethidine oxidation. We conclude that the mitochondria-targeting decylTPP moiety is responsible for the observed effects and advocate that every study employing alkylTPP-mediated mitochondrial targeting should routinely include control experiments with the corresponding alkylTPP moiety. |
| Databáze: | OpenAIRE |
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