PMID- 31498082
OWN - NLM
STAT- MEDLINE
DCOM- 20200131
LR  - 20210110
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 8
DP  - 2019 Sep 9
TI  - Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic 
      Ca(2).
LID - 10.7554/eLife.49682 [doi]
LID - e49682
AB  - 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 Ca(2+)-antagonized mechanism, or CaATiER (Ca(2+)-Antagonized 
      Transport into ER). Significantly, we show that mitochondria supply ATP to the ER 
      and a SERCA-dependent Ca(2+) 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 Ca(2+) 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.
CI  - (c) 2019, Yong et al.
FAU - Yong, Jing
AU  - Yong J
AUID- ORCID: 0000-0002-4970-408X
AD  - Degenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, United 
      States.
FAU - Bischof, Helmut
AU  - Bischof H
AUID- ORCID: 0000-0003-2380-600X
AD  - Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical 
      University of Graz, Graz, Austria.
FAU - Burgstaller, Sandra
AU  - Burgstaller S
AD  - Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical 
      University of Graz, Graz, Austria.
FAU - Siirin, Marina
AU  - Siirin M
AD  - Degenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, United 
      States.
FAU - Murphy, Anne
AU  - Murphy A
AD  - Department of Pharmacology, University of California, San Diego, La Jolla, United 
      States.
FAU - Malli, Roland
AU  - Malli R
AUID- ORCID: 0000-0001-6327-8729
AD  - Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical 
      University of Graz, Graz, Austria.
FAU - Kaufman, Randal J
AU  - Kaufman RJ
AUID- ORCID: 0000-0003-4277-316X
AD  - Degenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, United 
      States.
AD  - Department of Pharmacology, University of California, San Diego, La Jolla, United 
      States.
LA  - eng
GR  - R37DK042394/DK/NIDDK NIH HHS/United States
GR  - P30CA030199/CA/NCI NIH HHS/United States
GR  - R24 DK110973/DK/NIDDK NIH HHS/United States
GR  - R37 DK042394/DK/NIDDK NIH HHS/United States
GR  - P30 CA030199/CA/NCI NIH HHS/United States
GR  - R01AG062190/AG/NIA NIH HHS/United States
GR  - R01 HL052173/HL/NHLBI NIH HHS/United States
GR  - R01 DK113171/DK/NIDDK NIH HHS/United States
GR  - P28529-B27/Austrian Science Fund/International
GR  - R01DK113171/DK/NIDDK NIH HHS/United States
GR  - R01 CA198103/CA/NCI NIH HHS/United States
GR  - P 28529/FWF_/Austrian Science Fund FWF/Austria
GR  - R01 AG062190/AG/NIA NIH HHS/United States
GR  - R24DK110973/DK/NIDDK NIH HHS/United States
GR  - R01CA198103/CA/NCI NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - R01HL052173/HL/NHLBI NIH HHS/United States
GR  - R01DK103185/DK/NIDDK NIH HHS/United States
GR  - R01 DK103185/DK/NIDDK NIH HHS/United States
GR  - P30DK063491/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190909
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Cations, Divalent)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Biological Transport
MH  - Calcium/*metabolism
MH  - Cations, Divalent/metabolism
MH  - Cell Line
MH  - Cricetulus
MH  - Endoplasmic Reticulum/*metabolism
MH  - Humans
MH  - Mitochondria/*metabolism
MH  - Rats
PMC - PMC6763289
OTO - NOTNLM
OT  - ATP and adenosine nucleotides transport
OT  - Chinese hamster ovary cell
OT  - ER stress
OT  - SLC35B1/AXER protein
OT  - biochemistry
OT  - cell biology
OT  - chemical biology
OT  - organelle bioenergetics
OT  - protein folding
COIS- JY, HB, SB, MS, AM, RM, RK No competing interests declared
EDAT- 2019/09/10 06:00
MHDA- 2020/02/01 06:00
PMCR- 2019/09/09
CRDT- 2019/09/10 06:00
PHST- 2019/06/26 00:00 [received]
PHST- 2019/09/09 00:00 [accepted]
PHST- 2019/09/10 06:00 [pubmed]
PHST- 2020/02/01 06:00 [medline]
PHST- 2019/09/10 06:00 [entrez]
PHST- 2019/09/09 00:00 [pmc-release]
AID - 49682 [pii]
AID - 10.7554/eLife.49682 [doi]
PST - epublish
SO  - Elife. 2019 Sep 9;8:e49682. doi: 10.7554/eLife.49682.