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A systematic genetic interaction map of human solute carriers assigns a role to SLC25A51/MCART1 in mitochondrial NAD uptake

View ORCID ProfileEnrico Girardi, View ORCID ProfileGiuseppe Fiume, View ORCID ProfileUlrich Goldmann, View ORCID ProfileCeline Sin, Felix Müller, Sabrina Lindinger, View ORCID ProfileVitaly Sedlyarov, Ismet Srndic, View ORCID ProfileBenedikt Agerer, View ORCID ProfileFelix Kartnig, Eva Meixner, View ORCID ProfileAnna Skucha, View ORCID ProfileManuele Rebsamen, View ORCID ProfileAndreas Bergthaler, View ORCID ProfileJörg Menche, View ORCID ProfileGiulio Superti-Furga
doi: https://doi.org/10.1101/2020.08.31.275818
Enrico Girardi
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Giuseppe Fiume
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Ulrich Goldmann
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Celine Sin
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Felix Müller
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Sabrina Lindinger
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Vitaly Sedlyarov
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Ismet Srndic
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Benedikt Agerer
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Felix Kartnig
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Eva Meixner
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Anna Skucha
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Manuele Rebsamen
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Andreas Bergthaler
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Jörg Menche
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
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Giulio Superti-Furga
1CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
2Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
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  • For correspondence: gsuperti@cemm.oeaw.ac.at
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Abstract

Solute Carriers (SLCs) represent the largest family of human transporter proteins, consisting of more than 400 members1,2. Despite the importance of these proteins in determining metabolic states and adaptation to environmental changes, a large proportion of them is still orphan and lacks associated substrates1,3,4. Here we describe a systematic mapping of genetic interactions among SLCs in human cells. Network-based identification of correlated genetic interaction profile neighborhoods resulted in initial functional assignments to dozens of previously uncharacterized SLCs. Focused validation identified SLC25A51/MCART1 as the SLC enabling mitochondrial import of NAD(H). This functional interaction map of the human transportome offers a route for systematic integration of transporter function with metabolism and provides a blueprint for elucidation of the dark genome by biochemical and functional categories.

Competing Interest Statement

The authors have declared no competing interest.

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  • http://sigil.cemm.at

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 01, 2020.
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A systematic genetic interaction map of human solute carriers assigns a role to SLC25A51/MCART1 in mitochondrial NAD uptake
Enrico Girardi, Giuseppe Fiume, Ulrich Goldmann, Celine Sin, Felix Müller, Sabrina Lindinger, Vitaly Sedlyarov, Ismet Srndic, Benedikt Agerer, Felix Kartnig, Eva Meixner, Anna Skucha, Manuele Rebsamen, Andreas Bergthaler, Jörg Menche, Giulio Superti-Furga
bioRxiv 2020.08.31.275818; doi: https://doi.org/10.1101/2020.08.31.275818
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A systematic genetic interaction map of human solute carriers assigns a role to SLC25A51/MCART1 in mitochondrial NAD uptake
Enrico Girardi, Giuseppe Fiume, Ulrich Goldmann, Celine Sin, Felix Müller, Sabrina Lindinger, Vitaly Sedlyarov, Ismet Srndic, Benedikt Agerer, Felix Kartnig, Eva Meixner, Anna Skucha, Manuele Rebsamen, Andreas Bergthaler, Jörg Menche, Giulio Superti-Furga
bioRxiv 2020.08.31.275818; doi: https://doi.org/10.1101/2020.08.31.275818

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