SLC35B1 is AXER, an ATP/ADP exchanger in the ER membrane and part of a regulatory circuit
Description
The endoplasmic reticulum (ER) requires a constant ATP supply. However, the carrier that catalyzes ATP uptake into the ER was unknown. In search of the elusive ATP/ADP carrier we screened gene expression datasets for member(s) of the family of solute carriers that are co-expressed with BiP, the major ER resident ATP consumer, and are ER membrane proteins. We identified SLC35B1 as a potential candidate. Heterologous expression of SLC35B1 in E. coli revealed that SLC35B1 is highly specific for ATP and ADP and acts in antiport mode. Moreover, siRNA mediated depletion of SLC35B1 from HeLa cells reduced ER ATP levels and BiP activity. Thus, human SLC35B1 provides ATP to the ER and was named AXER (ATP/ADP exchanger in the ER membrane). Furthermore, we began to unravel an ER to cytosol low energy response regulatory axis (termed lowER) that is central for maintaining ER ATP supply under steady state and stress conditions. This work is about to be published under the title AXER is an ATP/ADP exchanger in the membrane of the endoplasmic reticulum by Marie-Christine Klein, Katharina Zimmermann, Stefan Schorr, Martina Landini, Patrick A. W. Klemens, Jacqueline Altensell, Martin Jung, Elmar Krause, Duy Nguyen, Volkhard Helms, Jens Rettig, Claudia Fecher-Trost, Adolfo Cavalié, Markus Hoth, Ivan Bogeski, H. Ekkehard Neuhaus, Richard Zimmermann, Sven Lang and Ilka Haferkamp Here we present the original western blot data.