**5. Conclusions**

The data in the present study showed different effects of palmitate and oleate on oxygen utilization in myoblasts of both m.3243A>G patients and controls. The myoblasts, indeed, showed similar ß-oxidation values using palmitate or oleate as substrate. However, the presence of excessive palmitate showed a negative effect on respiratory rates of patients. This could confirm the already reported negative effect of excessive palmitate on mitochondrial function in other studies. Since saturated fatty acids increase the insulin resistance, these results might reveal why the patients harboring the m.3243A>G mutation have a higher risk for developing of diabetes type II.

Limitations: the study was performed on a small study population. In particular, in the case of the 70-year-old patient listed in the cohort, the aging might have an effect on mitochondrial dysfunction. However, it has to be noticed that mitochondrial diseases are rare diseases with a huge variety of mutations and the present study should be considered as a pilot one; it is not always responsible to perform a tissue/muscle biopsy. It is known that patients harboring the m.3243A>G mutation have a higher risk of developing diabetes mellitus. However, in the present study, only one patient is diagnosed with diabetes mellitus (Patient P1).

**Author Contributions:** Conceptualization, L.M.S., H.S., S.Z.; methodology, L.M.S., H.S., S.A.-R., A.T.; software, L.M.S., D.L.U., H.S., S.A.-R.; data curation, L.M.S., D.L.U., H.S., S.A.-R.; writing—original draft preparation, L.M.S., D.L.U.; writing—review and editing, L.M.S., H.S., S.A.-R., A.T.; D.L.U.; S.Z.; project administration, L.M.S., S.Z. All authors have read and agreed to the published version of the manuscript.

**Funding:** D.L.U. is funded by the Hertha-Nathorff-Programm (HNP) of the Medical University of Ulm, Germany.

**Acknowledgments:** We thank the Muscle Tissue Culture Collection (MTCC) at the University Hospital of Munich Muenchen for providing the samples, and Julia Emmerich for excellent technical assistance. The Muscle Tissue Culture Collection is part of the German network on muscular dystrophies (MD-NET) and the German network for mitochondrial disorders (mito-NET, 01GM1113A) funded by the German Ministry of Education and Research (BMBF, Bonn, Germany). The Muscle Tissue Culture Collection is a partner of EuroBioBank (www.eurobiobank.org) and TREAT-NMD (www.treat-nmd.eu). L.M.S., D.L.U., and S.Z. are members of the German mitoNET funded by the German Ministry of Education and Research. We thank the Center of Basic Medical Research (ZMG) of the medical school at the University of Halle-Wittenberg for providing the Seahorse device. We acknowledge the financial support within the funding program Open Access Publishing by the German Research Foundation (DFG).

**Conflicts of Interest:** The authors declare no conflict of interest.
