Evidence map›Paper›PMID 31268780›Full record

ArticleAmerican journal of physiology. Cell physiology2019

G protein-coupled receptor kinase 2 regulates mitochondrial bioenergetics and impairs myostatin-mediated autophagy in muscle cells.

Leandro Henrique Manfredi, Joshur Ang, Nesibe Peker, Ruben K Dagda, Craig McFarlane

Open access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. GRK2 and Mitochondrial Dynamics in Cardiovascular Health and Disease.International journal of molecular sciences · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Regulation of Myostatin on the Growth and Development of Skeletal Muscle.Frontiers in cell and developmental biology · 2021
    Review
  12. Article
  13. Irisin and Autophagy: First Update.International journal of molecular sciences · 2020
    Review
  14. Review
  15. 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

5 authors at 3 institutions in 4 countries.

Leandro Henrique ManfrediDepartment of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Joshur AngSingapore Institute for Clinical Sciences, Agency for Science, Technology, and Research (A*STAR), Brenner Centre for Molecular Medicine, Singapore.
Nesibe PekerSchool of Biological Sciences, Nanyang Technological University, Singapore.
Ruben K DagdaDepartment of Pharmacology, School of Medicine, University of Nevada, Reno, Nevada.
Craig McFarlaneSingapore Institute for Clinical Sciences, Agency for Science, Technology, and Research (A*STAR), Brenner Centre for Molecular Medicine, Singapore.ORCID 0000-0002-7056-8887
Agency for Science, Technology and Research · SGNanyang Technological University · SGUniversity of Nevada, Reno · US

Funding

Cell Biology of Signaling across MembranesP20GM103554 · NIGMS · UNIVERSITY OF NEVADA RENO · PI VON BARTHELD, CHRISTOPHER S · 2012 to 2016
$8.0M
Regulation of Dendrite Homeostasis by PINK1 and PKA in Models of Parkinson's DiseaseR01NS105783 · NINDS · UNIVERSITY OF NEVADA RENO · PI DAGDA, RUBEN K · 2018 to 2022
$1.9M
NIGMS NIH HHS P20 GM103554NINDS NIH HHS R01 NS105783
6 · The paper itself

Abstract

G protein-coupled receptor kinase 2 (GRK2) is an important protein involved in β-adrenergic receptor desensitization. In addition, studies have shown GRK2 can modulate different metabolic processes in the cell. For instance, GRK2 has been recently shown to promote mitochondrial biogenesis and increase ATP production. However, the role of GRK2 in skeletal muscle and the signaling mechanisms that regulate GRK2 remain poorly understood. Myostatin is a well-known myokine that has been shown to impair mitochondria function. Here, we have assessed the role of myostatin in regulating GRK2 and the subsequent downstream effect of myostatin regulation of GRK2 on mitochondrial respiration in skeletal muscle. Myostatin treatment promoted the loss of GRK2 protein in myoblasts and myotubes in a time- and dose-dependent manner, which we suggest was through enhanced ubiquitin-mediated protein loss, as treatment with proteasome inhibitors partially rescued myostatin-mediated loss of GRK2 protein. To evaluate the effects of GRK2 on mitochondrial respiration, we generated stable myoblast lines that overexpress GRK2. Stable overexpression of GRK2 resulted in increased mitochondrial content and enhanced mitochondrial/oxidative respiration. Interestingly, although overexpression of GRK2 was unable to prevent myostatin-mediated impairment of mitochondrial respiratory function, elevated levels of GRK2 blocked the increased autophagic flux observed following treatment with myostatin. Overall, our data suggest a novel role for GRK2 in regulating mitochondria mass and mitochondrial respiration in skeletal muscle.

Indexed as

AnimalsAutophagyG-Protein-Coupled Receptor Kinase 2MiceMitochondriaMuscle CellsMuscle, SkeletalMyoblastsMyostatinReceptors, Adrenergic, betaReceptors, Adrenergic, beta-2Signal TransductionG-Protein-Coupled Receptor Kinase 2MyostatinReceptors, Adrenergic, betaReceptors, Adrenergic, beta-2autophagyGRK2mitochondriamyoblastmyostatin

Identifiers

PMID31268780
PMCPMC6850988
OpenAlexW2954868555

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.