Sep 10, 2019

Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic Ca2

ELife
Jing YongRandal J Kaufman

Abstract

The endoplasmic reticulum (ER) imports ATP and uses energy from ATP hydrolysis for protein folding and trafficking. However, little is known about how this vital ATP transport occurs across the ER membrane. Here, using three commonly used cell lines (CHO, INS1 and HeLa), we report that ATP enters the ER lumen through a cytosolic Ca2+-antagonized mechanism, or CaATiER (Ca2+-Antagonized Transport into ER). Significantly, we show that mitochondria supply ATP to the ER and a SERCA-dependent Ca2+ gradient across the ER membrane is necessary for ATP transport into the ER, through SLC35B1/AXER. We propose that under physiological conditions, increases in cytosolic Ca2+ inhibit ATP import into the ER lumen to limit ER ATP consumption. Furthermore, the ATP level in the ER is readily depleted by oxidative phosphorylation (OxPhos) inhibitors and that ER protein misfolding increases ATP uptake from mitochondria into the ER. These findings suggest that ATP usage in the ER may increase mitochondrial OxPhos while decreasing glycolysis, i.e. an 'anti-Warburg' effect.

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Mentioned in this Paper

ATP Transport
Inhibitors
Uptake
Calcium ion
Trafficking
Oxidative Phosphorylation
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Ins1 protein, mouse
HelA protein, bacteria
Adenosine Triphosphate

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