Talk:Koopman 2022 Abstract Bioblast
Comments by the Reviewer
Moreno-Sanchez Rafael 2022-06-02
- There are some important missing details, which should be added to make a more informative and interesting abstract. The concentrations used of the Trolox- and CoQ-decylTPP+ conjugated molecules must be clearly indicated, as well as the vehicle used to dissolve these molecules. Likewise, the quantitative percentual effects of these conjugates could also be explicitly disclosed instead of just stating the qualitative adjectives “reduced” C1 activity, “lowered” supercomplexes, “inhibited” O2 consumption.
Koopman Werner JH 2022-06-4
- Thanks for your comments and for the opportunity to revise the abstract. I did not include absolute numbers regarding the changes observed but now indicated that all were significant. → Version 2
- Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP+) cations is a widely applied key technology 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 system (ETS), 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 did not greatly affect cell viability.
- Unexpectedly, this treatment reduced CI levels/activity, lowered the amount of ETS supercomplexes, inhibited mitochondrial oxygen consumption, increased extracellular acidification, altered mitochondrial morphology and stimulated the levels of hydroethidine-oxidizing ROS.
- 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.