2. Academic Validation
  3. Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

  • Nat Commun. 2020 Dec 1;11(1):6145. doi: 10.1038/s41467-020-19871-x.
Enrico Girardi 1,  Gennaro Agrimi 2,  Ulrich Goldmann 1,  Giuseppe Fiume 1,  Sabrina Lindinger 1,  Vitaly Sedlyarov 1,  Ismet Srndic 1,  Bettina Gürtl 1,  Benedikt Agerer 1,  Felix Kartnig 1,  Pasquale Scarcia 2,  Maria Antonietta Di Noia 2,  Eva Liñeiro 1,  Manuele Rebsamen 1,  Tabea Wiedmer 1,  Andreas Bergthaler 1,  Luigi Palmieri 2 3,  Giulio Superti-Furga 4 5
Affiliations

Affiliations

  • 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 2 Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
  • 3 CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), Bari, Italy.
  • 4 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. [email protected].
  • 5 Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. [email protected].
PMID: 33262325 DOI: 10.1038/s41467-020-19871-x
Abstract

About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction-driven functional gene deorphanization.

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