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

Author

Listed:
  • 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
    CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM))

  • Giulio Superti-Furga

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Medical University of Vienna)

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.

Suggested Citation

  • Enrico Girardi & Gennaro Agrimi & Ulrich Goldmann & Giuseppe Fiume & Sabrina Lindinger & Vitaly Sedlyarov & Ismet Srndic & Bettina Gürtl & Benedikt Agerer & Felix Kartnig & Pasquale Scarcia & Maria An, 2020. "Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19871-x
    DOI: 10.1038/s41467-020-19871-x
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    Cited by:

    1. Sook Wah Yee & Luis Ferrández-Peral & Pol Alentorn-Moron & Claudia Fontsere & Merve Ceylan & Megan L. Koleske & Niklas Handin & Virginia M. Artegoitia & Giovanni Lara & Huan-Chieh Chien & Xujia Zhou &, 2024. "Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Xiaojian Shi & Bryn Reinstadler & Hardik Shah & Tsz-Leung To & Katie Byrne & Luanna Summer & Sarah E. Calvo & Olga Goldberger & John G. Doench & Vamsi K. Mootha & Hongying Shen, 2022. "Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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