AXER is an ATP/ADP exchanger in the membrane of the endoplasmic reticulum

Nature Communications
Marie-Christine KleinIlka Haferkamp

Abstract

To fulfill its role in protein biogenesis, the endoplasmic reticulum (ER) depends on the Hsp70-type molecular chaperone BiP, which requires a constant ATP supply. However, the carrier that catalyzes ATP uptake into the ER was unknown. Here, we report that our screen of gene expression datasets for member(s) of the family of solute carriers that are co-expressed with BiP and are ER membrane proteins identifies SLC35B1 as a potential candidate. Heterologous expression of SLC35B1 in E. coli reveals that SLC35B1 is highly specific for ATP and ADP and acts in antiport mode. Moreover, depletion of SLC35B1 from HeLa cells reduces ER ATP levels and, as a consequence, BiP activity. Thus, human SLC35B1 may provide ATP to the ER and was named AXER (ATP/ADP exchanger in the ER membrane). Furthermore, we propose an ER to cytosol low energy response regulatory axis (termed lowER) that appears as central for maintaining ER ATP supply.

Associated Datasets

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Citations

Feb 19, 2019·Parasitology·Giulia BandiniFrançoise H Routier
Jul 22, 2019·FEBS Letters·Sarah HaßdenteufelRichard Zimmermann
Jul 16, 2019·The Journal of Clinical Investigation·Li-Chuan ChanMien-Chie Hung
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May 8, 2020·Journal of Oncology·Shu-Man LiDan Xie
Jan 1, 2020·Clinical Proteomics·Jaimie DufresneJohn G Marshall
Jun 13, 2020·Frontiers in Endocrinology·Jennyfer MartínezCelia Quijano
May 22, 2019·Nature Cell Biology·Roland Malli, Wolfgang F Graier
Aug 28, 2020·Biomolecules·Adriano Nunes-NesiAlisdair R Fernie
Dec 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Logan K TownsendDavid C Wright
Aug 30, 2019·Computational and Structural Biotechnology Journal·Barbara HadleyJoe Tiralongo
Jan 19, 2021·The Journal of Biological Chemistry·Ave EesmaaMart Saarma
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Apr 30, 2021·Biomedical Materials·Shanni HongYi Lu
Jun 25, 2021·Nature Reviews. Endocrinology·Jing YongRandal J Kaufman
Aug 27, 2021·The FEBS Journal·Seyta Ley-Ngardigal, Giulia Bertolin

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Datasets Mentioned

BETA
CAC35849
CAB46704.1
CAA97965

Methods Mentioned

BETA
fluorescence imaging
super-resolution microscopy
immunoprecipitation
transfection
FRET
fluorescence microscopy
PCR
X-ray
Assay

Software Mentioned

AxioVision
NAMD
- CAP
FUSION
Phyre2
AXER
Babel
TILLvisION
AutoDock4
RaptorX

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