**5. Conclusions**

In conclusion, we here report a new mtDNA variant in the *ATP6* gene (m.8909T>C) and provide evidence using the yeast model that it has detrimental consequences on ATP synthase similar to those of other *ATP6* mutations with a well-established pathogenicity like m.9176T>C and m.8993T>C. On this basis, it is a reasonable assumption that this variant has the potential to compromise human health. Our work illustrates the power of yeast to help the study of specific human mtDNA variants found in heterogeneous genetic backgrounds and comprehension of human diseases linked to this DNA.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2075-1729/10/9/215/s1, Figure S1: Occurrence of renal failure during follow-up of 35 previously reported m.3243G>A patients diagnosed with a nephrotic syndrome, Table S1: Mean clinical characteristics of 35 previously reported m.3243G>A patients diagnosed with a nephrotic syndrome, Table S2. Individual clinical characteristics of 35 previously reported m.3243G>A patients diagnosed with a nephrotic syndrome References [59–81] are cited in the supplementary materials.

**Author Contributions:** Data analysis and interpretation and manuscript writing, Q.D.; construction and properties of yeast strains, R.K., X.S., M.B. and K.G.; patient recruitment, experiment performance, data analysis and interpretation, drafting the work, W.Z.; experiment performance and data analysis and interpretation, K.N.; patient recruitment, counseling and follow-up, W.Z.; structural modeling and data interpretation and manuscript editing, A.D. and M.-F.G.; patient recruitment, counseling and follow-up, S.X.; laboratory analysis and interpretation, M.Z.; patient selection, H.X.; histological analysis and interpretation, C.Z.; study design, patient selection and clinical analysis and interpretation, Z.L.; study design and coordination, data interpretation and manuscript writing, J.P.d.R., H.C. and D.T.-T. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was supported by the National Natural Science Foundation (NSF 81611130131 & 81570714) to H.C., the Association Française contre les Myopathie (AFM 22382) to DTT, the Agence Nationale de la Recherche (ANR-12-BSV8-024) to M.-F.G. and A.D., and by the National Science Center of Poland (UMO-2013/11/B/NZ1/02102) to R.K.

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

**Ethical Approval Number:** 2018NL-013. Participants signed a patient consent form for article containing patient details and/or images.
