Evidence map›Paper›PMID 35998642›Full record

ArticleCell stem cell2022

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells.

Nicole Baker, Steven Wade, Matthew Triolo, John Girgis, Damian Chwastek, Sarah Larrigan, Peter Feige, Ryo Fujita, Colin Crist, Michael A Rudnicki and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  13. Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025
    Review
  14. Article
  15. Review
  16. The dynamics of centromere assembly and disassembly during quiescence.bioRxiv : the preprint server for biology · 2025
    Article
  17. Molecular mechanisms of mitochondrial quality control.Translational neurodegeneration · 2025
    Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Nicole BakerDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Steven WadeDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Matthew TrioloDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
John GirgisDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Damian ChwastekDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Sarah LarriganDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Peter FeigeSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
Ryo FujitaLady Davis Institute for Medical Research, Jewish General Hospital, Department of Human Genetics, McGill University, Montreal, QC H3T 1E2, Canada; Division of Regenerative Medicine, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
Colin CristLady Davis Institute for Medical Research, Jewish General Hospital, Department of Human Genetics, McGill University, Montreal, QC H3T 1E2, Canada.
Michael A RudnickiSprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
Yan BurelleInterdisciplinary School of Health Sciences, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mireille KhachoDepartment of Biochemistry, Microbiology and Immunology, Center for Neuromuscular Disease (CNMD), Ottawa Institute of Systems Biology (OISB), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: mkhacho@uottawa.ca.
University of Ottawa · CAJewish General Hospital · CA

Funding

GENETIC REGULATION OF SKELETAL MUSCLE REPAIRR01AR044031 · NIAMS · OTTAWA HOSPITAL RESEARCH INSTITUTE · PI RUDNICKI, MICHAEL A · 1996 to 2025
$5.6M
NIAMS NIH HHS R01 AR044031
6 · The paper itself

Abstract

Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.

Indexed as

Adult Stem CellsMitochondrial ProteinsMitochondrial DynamicsMusclesMyoblastsMitochondrial Proteinsadult muscle stem cellsagingG-alertglutathioneGSHmitochondrial dynamicsmTOROPA1quiescencereactive oxygen speciesROSstem cell activationstem cell maintenancesystemic factors

Identifiers

PMID35998642
PMCPMC10249109
OpenAlexW4292646795

What OpenQuestion holds

Textmetadata
LicenceTDM
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.