**6. Concluding Remarks**

Mammalian mitochondrial DNA codes for 13 proteins, all of which are subunits of the respiratory complexes and ATP synthase. Most of the organelle, however, is encoded in the nuclear genome, by what, in yeast, is estimated to be at least 900 genes or 15% of the genome. It stands to reason that a large number of human genetic disorders will stem from mutations that affect mitochondrial function. In the past, studies of yeast *pet* mutants have had a direct impact on understanding the genetic and mechanistic basis of human mitochondrial diseases. However, about 20% of the eukaryotic proteome has not yet been characterized, even in well-studied model organisms such as *S. cerevisiae* [302]. A substantial number of proteins still lacking an ascribed function are encoded by genes that affect mitochondrial respiration. In this context, yeast is still a powerful platform for discovering the function of uncharacterized mitochondrial proteins, as well as to gain a better understanding of the underlying molecular consequences of pathogenic mutations that could prove to be promising targets for mitochondrial disease therapies.

**Author Contributions:** Conceptualization: L.V.R.F.; writing: L.V.R.F., L.B., and M.H.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** L.V.R.F. was supported by FAPESP Post-Doctoral Fellowship 2019/02799-2.

**Acknowledgments:** The authors would like to express gratitude for the guidance of Alexander Tzagoloff in the preparation of this manuscript.

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