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

Enrico Girardi, Gennaro Agrimi, Ulrich Goldmann, Giuseppe Fiume, Sabrina Lindinger, Vitaly Sedlyarov, Ismet Srndic, Bettina Gürtl, Benedikt Agerer, Felix Kartnig, Pasquale Scarcia, Maria Antonietta Di Noia, Eva Liñeiro, Manuele Rebsamen, Tabea Wiedmer, Andreas Bergthaler, Luigi Palmieri and Giulio Superti-Furga ()
Additional contact information
Enrico Girardi: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Gennaro Agrimi: University of Bari
Ulrich Goldmann: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Giuseppe Fiume: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Sabrina Lindinger: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Vitaly Sedlyarov: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Ismet Srndic: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Bettina Gürtl: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Benedikt Agerer: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Felix Kartnig: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Pasquale Scarcia: University of Bari
Maria Antonietta Di Noia: University of Bari
Eva Liñeiro: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Manuele Rebsamen: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Tabea Wiedmer: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Andreas Bergthaler: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Luigi Palmieri: University of Bari
Giulio Superti-Furga: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19871-x

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