Evidence map›Paper›PMID 36899830›Full record

ArticleCells2023

Real-Time Visualization of Cytosolic and Mitochondrial ATP Dynamics in Response to Metabolic Stress in Cultured Cells.

Donnell White, Lothar Lauterboeck, Parnia Mobasheran, Tetsuya Kitaguchi, Antoine H Chaanine, Qinglin Yang

Open access · goldFull text read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Donnell WhiteCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.ORCID 0000-0002-5368-3752
Lothar LauterboeckCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.ORCID 0000-0001-5606-1767
Parnia MobasheranCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Tetsuya KitaguchiLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Kanagawa, Japan.
Antoine H ChaanineHealthPartners Group, Regions Hospital, Saint Paul, MN 55101, USA.
Qinglin YangCardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.ORCID 0000-0002-6024-2517
Louisiana State University Health Sciences Center New Orleans · USRegions Hospital · USThermo Fisher Scientific (United States) · USTokyo Institute of Technology · JP

Funding

Energetic State and Metabolic Remodeling in Cardiac Hypertrophy and FailureR01HL160969 · NHLBI · LSU HEALTH SCIENCES CENTER · PI YANG, QINGLIN · 2022 to 2025
$1.9M
Improving Mitochondrial Function to Protect against Myocardial Ischemia/ReperfusionR01HL135336 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YANG, QINGLIN · 2017 to 2020
$1.5M
NHLBI NIH HHS R01 HL135336NHLBI NIH HHS R01 HL160969
6 · The paper itself

Abstract

Adenosine 5' triphosphate (ATP) is the energy currency of life, which is produced in mitochondria (~90%) and cytosol (less than 10%). Real-time effects of metabolic changes on cellular ATP dynamics remain indeterminate. Here we report the design and validation of a genetically encoded fluorescent ATP indicator that allows for real-time, simultaneous visualization of cytosolic and mitochondrial ATP in cultured cells. This dual-ATP indicator, called smacATPi (simultaneous mitochondrial and cytosolic ATP indicator), combines previously described individual cytosolic and mitochondrial ATP indicators. The use of smacATPi can help answer biological questions regarding ATP contents and dynamics in living cells. As expected, 2-deoxyglucose (2-DG, a glycolytic inhibitor) led to substantially decreased cytosolic ATP, and oligomycin (a complex V inhibitor) markedly decreased mitochondrial ATP in cultured HEK293T cells transfected with smacATPi. With the use of smacATPi, we can also observe that 2-DG treatment modestly attenuates mitochondrial ATP and oligomycin reduces cytosolic ATP, indicating the subsequent changes of compartmental ATP. To evaluate the role of ATP/ADP carrier (AAC) in ATP trafficking, we treated HEK293T cells with an AAC inhibitor, Atractyloside (ATR). ATR treatment attenuated cytosolic and mitochondrial ATP in normoxia, suggesting AAC inhibition reduces ADP import from the cytosol to mitochondria and ATP export from mitochondria to cytosol. In HEK293T cells subjected to hypoxia, ATR treatment increased mitochondrial ATP along with decreased cytosolic ATP, implicating that ACC inhibition during hypoxia sustains mitochondrial ATP but may not inhibit the reversed ATP import from the cytosol. Furthermore, both mitochondrial and cytosolic signals decrease when ATR is given in conjunction with 2-DG in hypoxia. Thus, real-time visualization of spatiotemporal ATP dynamics using smacATPi provides novel insights into how cytosolic and mitochondrial ATP signals respond to metabolic changes, providing a better understanding of cellular metabolism in health and disease.

Indexed as

Adenosine TriphosphateStress, PhysiologicalAdenosine DiphosphateAtractylosideCytosolHEK293 CellsHumansOligomycinsAdenosine DiphosphateAdenosine TriphosphateAtractylosideOligomycinsATPbiosensorfluorescencemetabolismmitochondria

Identifiers

PMID36899830
PMCPMC10000496
OpenAlexW4321496092

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read58
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.