Evidence map›Paper›PMID 24884163›Full record

ArticleBiochemistry2014

Adenine nucleotide translocase is acetylated in vivo in human muscle: Modeling predicts a decreased ADP affinity and altered control of oxidative phosphorylation.

Clinton Mielke, Natalie Lefort, Carrie G McLean, Jeanine M Cordova, Paul R Langlais, Andrew J Bordner, Jerez A Te, S Banu Ozkan, Wayne T Willis, Lawrence J Mandarino

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

30 citing papers in PubMed, 52 citations in OpenAlex.

  1. Trial
  2. Relaxin-2: Shaping the Proteomic Landscape of Skeletal Muscle Physiology, Glucose Trafficking, and Mitochondrial Function in Rat.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. Review
  4. Article
  5. Article
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  9. Article
  10. Article
  11. Targeting skeletal muscle mitochondrial health in obesity.Clinical science (London, England : 1979) · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  18. Oxidative phosphorylation KBiochimica et biophysica acta. Bioenergetics · 2021
    Article
  19. Review
  20. Review
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

10 authors at 2 institutions in 1 country.

Clinton MielkeCenter for Metabolic and Vascular Biology, Arizona State University , Tempe, Arizona 85004, United States.
Natalie Lefort
Carrie G McLean
Jeanine M Cordova
Paul R Langlais
Andrew J Bordner
Jerez A Te
S Banu Ozkan
Wayne T Willis
Lawrence J Mandarino
Arizona State University · USMayo Clinic in Arizona · US

Funding

MOLECULAR REGULATION OF MUSCLE GLUCOSE METABOLISM IN MANR01DK047936 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI MANDARINO, LAWRENCE J · 1994 to 2022
$10.7M
PGC-1 & Muscle Mitochondrial Dysfunction in DiabetesR01DK066483 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI MANDARINO, LAWRENCE J · 2004 to 2018
$6.7M
NIDDK NIH HHS DK066483NIDDK NIH HHS R01 DK047936
6 · The paper itself

Abstract

Proteomics techniques have revealed that lysine acetylation is abundant in mitochondrial proteins. This study was undertaken (1) to determine the relationship between mitochondrial protein acetylation and insulin sensitivity in human skeletal muscle, identifying key acetylated proteins, and (2) to use molecular modeling techniques to understand the functional consequences of acetylation of adenine nucleotide translocase 1 (ANT1), which we found to be abundantly acetylated. Eight lean and eight obese nondiabetic subjects had euglycemic clamps and muscle biopsies for isolation of mitochondrial proteins and proteomics analysis. A number of acetylated mitochondrial proteins were identified in muscle biopsies. Overall, acetylation of mitochondrial proteins was correlated with insulin action (r = 0.60; P < 0.05). Of the acetylated proteins, ANT1, which catalyzes ADP-ATP exchange across the inner mitochondrial membrane, was acetylated at lysines 10, 23, and 92. The extent of acetylation of lysine 23 decreased following exercise, depending on insulin sensitivity. Molecular dynamics modeling and ensemble docking simulations predicted the ADP binding site of ANT1 to be a pocket of positively charged residues, including lysine 23. Calculated ADP-ANT1 binding affinities were physiologically relevant and predicted substantial reductions in affinity upon acetylation of lysine 23. Insertion of these derived binding affinities as parameters into a complete mathematical description of ANT1 kinetics predicted marked reductions in adenine nucleotide flux resulting from acetylation of lysine 23. Therefore, acetylation of ANT1 could have dramatic physiological effects on ADP-ATP exchange. Dysregulation of acetylation of mitochondrial proteins such as ANT1 therefore could be related to changes in mitochondrial function that are associated with insulin resistance.

Indexed as

Insulin ResistanceOxidative PhosphorylationProtein Processing, Post-TranslationalAcetylationAdenine Nucleotide Translocator 1Adenosine DiphosphateAdultBinding SitesBody Mass IndexDown-RegulationFemaleHumansLysineMaleMiddle AgedMitochondria, MuscleAdenine Nucleotide Translocator 1Adenosine DiphosphateLysineMuscle ProteinsSLC25A4 protein, human

Identifiers

PMID24884163
PMCPMC4067143
OpenAlexW2314015436

What OpenQuestion holds

Textmetadata
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.