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Study · In vitro (cells) · 2021

9 results

Mitofusion is required for MOTS-c induced GLUT4 translocation.

Bhullar KS, Shang N, Kerek E, Wu K, Wu J

Scientific reports12 Jul 2021Cited by 16 (Europe PMC)

PMID34253808 (opens in a new tab)PMCIDPMC8275580 (opens in a new tab)DOI10.1038/s41598-021-93735-2 (opens in a new tab)PepBankPUB-34253808
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Summary

MOTS-c (mitochondrial ORF of the twelve S-c) is a 16-amino-acid mitochondrial peptide that has been shown to counter insulin resistance and alleviate obesity in vivo. However, the mechanisms involved in the pharmacological action of MOTS-c remain elusive. Based on the ability of MOTS-c to improve insulin resistance and promote cold adaptation, we hypothesized that MOTS-c might play a role in boosting the number of mitochondria in a cell. We found that treatment of mammalian cells with MOTS-c increased protein levels of TFAM, COX4, and NRF1, which are markers for mitochondrial biogenesis. However, flow cytometry analysis using MitoTracker Green revealed a sharp reduction in the mitochondrial count after MOTS-c treatment. We then anticipated possible synchronized activation of mitofusion/mitochondrial fusion by MOTS-c following the onset of mitochondrial biogenesis. This was confirmed after a significant increase in protein levels two GTPases, OPA1, and MFN2, both vital for the fusion of mammalian mitochondria. Finally, we found that inhibition of the two GTPases by TNFα abrogated the ability of MOTS-c to prompt GLUT4 translocation and glucose uptake. Similar results were obtained by siRNA KD of MFN2 as well. Our results reveal for the first time a pathway that links mitofusion to MOTS-c-induced GLUT4 translocation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In mammalian cells, MOTS‑c treatment increased protein levels of TFAM, a marker of mitochondrial biogenesis.

    In plain wordsIn cells, MOTS‑c raised TFAM, a marker of new mitochondria.

    Peptide
    MOTS-c
    Outcome
    IncreaseTFAM protein level
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that treatment of mammalian cells with MOTS-c increased protein levels of TFAM, COX4, and NRF1, which are markers for mitochondrial biogenesis.
  2. 02LabIn vitro (cells)Mechanism

    In mammalian cells, MOTS‑c treatment increased protein levels of COX4, a marker of mitochondrial biogenesis.

    In plain wordsIn cells, MOTS‑c raised COX4, a marker of new mitochondria.

    Peptide
    MOTS-c
    Outcome
    IncreaseCOX4 protein level
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that treatment of mammalian cells with MOTS-c increased protein levels of TFAM, COX4, and NRF1, which are markers for mitochondrial biogenesis.
  3. 03LabIn vitro (cells)Mechanism

    In mammalian cells, MOTS‑c treatment increased protein levels of NRF1, a marker of mitochondrial biogenesis.

    In plain wordsIn cells, MOTS‑c raised NRF1, a marker of new mitochondria.

    Peptide
    MOTS-c
    Outcome
    IncreaseNRF1 protein level
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that treatment of mammalian cells with MOTS-c increased protein levels of TFAM, COX4, and NRF1, which are markers for mitochondrial biogenesis.
  4. 04LabIn vitro (cells)Mechanism

    In mammalian cells, flow cytometry with MitoTracker Green showed a sharp reduction in mitochondrial count after MOTS‑c treatment.

    In plain wordsIn cells, MOTS‑c treatment led to a sharp drop in the number of mitochondria.

    Peptide
    MOTS-c
    Outcome
    DecreaseMitochondrial count by MitoTracker Green
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, flow cytometry analysis using MitoTracker Green revealed a sharp reduction in the mitochondrial count after MOTS-c treatment.
  5. 05LabIn vitro (cells)Mechanism

    In mammalian cells, MOTS‑c significantly increased protein levels of the fusion GTPase OPA1.

    In plain wordsIn cells, MOTS‑c raised OPA1, a protein that helps mitochondria fuse.

    Peptide
    MOTS-c
    Outcome
    IncreaseOPA1 protein level
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    This was confirmed after a significant increase in protein levels two GTPases, OPA1, and MFN2, both vital for the fusion of mammalian mitochondria.
  6. 06LabIn vitro (cells)Mechanism

    In mammalian cells, MOTS‑c significantly increased protein levels of the fusion GTPase MFN2.

    In plain wordsIn cells, MOTS‑c raised MFN2, a protein that helps mitochondria fuse.

    Peptide
    MOTS-c
    Outcome
    IncreaseMFN2 protein level
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Mitochondrial function · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    This was confirmed after a significant increase in protein levels two GTPases, OPA1, and MFN2, both vital for the fusion of mammalian mitochondria.
  7. 07LabIn vitro (cells)Mechanism

    In mammalian cells, inhibition of the two fusion GTPases by TNFα abrogated the ability of MOTS‑c to prompt GLUT4 translocation.

    In plain wordsIn cells, when mitochondrial fusion proteins were blocked, MOTS‑c no longer moved the glucose transporter GLUT4 to the surface.

    Peptide
    MOTS-c
    Outcome
    No significant changeGLUT4 translocation when fusion GTPases were inhibited by TNFα
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Finally, we found that inhibition of the two GTPases by TNFα abrogated the ability of MOTS-c to prompt GLUT4 translocation and glucose uptake.
  8. 08LabIn vitro (cells)Mechanism

    In mammalian cells, inhibition of the two fusion GTPases by TNFα abrogated the ability of MOTS‑c to prompt glucose uptake.

    In plain wordsIn cells, when mitochondrial fusion proteins were blocked, MOTS‑c no longer increased glucose uptake.

    Peptide
    MOTS-c
    Outcome
    No significant changeGlucose uptake when fusion GTPases were inhibited by TNFα
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Finally, we found that inhibition of the two GTPases by TNFα abrogated the ability of MOTS-c to prompt GLUT4 translocation and glucose uptake.
  9. 09LabIn vitro (cells)Mechanism

    In mammalian cells, siRNA knockdown of MFN2 gave results similar to GTPase inhibition, abrogating MOTS‑c induced GLUT4 translocation and glucose uptake.

    In plain wordsIn cells, removing MFN2 also stopped MOTS‑c from moving GLUT4 and raising glucose uptake.

    Peptide
    MOTS-c
    Outcome
    No significant changeGLUT4 translocation and glucose uptake with MFN2 siRNA knockdown
    Study

    n: not reported in source

    Mammalian cells
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Similar results were obtained by siRNA KD of MFN2 as well.
    1 context sentence
    Summary · context
    Finally, we found that inhibition of the two GTPases by TNFα abrogated the ability of MOTS-c to prompt GLUT4 translocation and glucose uptake.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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