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Study · Animal study (in vivo) · mouse · 2021

4 results

Reduced adenosine diphosphate sensitivity in skeletal muscle mitochondria increases reactive oxygen species production in mouse models of aging and oxidative stress but not denervation.

Pharaoh G, Brown J, Ranjit R, Ungvari Z, Van Remmen H

JCSM rapid communications28 Dec 2020Cited by 23 (Europe PMC)

PMID36159599 (opens in a new tab)PMCIDPMC9503137 (opens in a new tab)DOI10.1002/rco2.29 (opens in a new tab)PepBankPUB-36159599
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Summary

BackgroundMitochondrial bioenergetics are sensitive to adenosine diphosphate (ADP) concentration. Reactive oxygen species (ROS) production and respiration [oxygen consumption rate (OCR)] are altered at physiological ADP concentrations (i.e. ADP insensitivity) in aged human muscle. Here, we investigate ADP sensitivity in mouse muscle mitochondria.MethodsWe measured OCR and ROS production in permeabilized gastrocnemius fibres using an ADP titration protocol and the Oroboros O2k respirometer and fluorometer. We measured changes in ADP sensitivity in muscle from mice at different ages, after sciatic nerve transection (denervation), and in response to increased oxidative stress (Sod1 -/- mice). Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the Sod1 -/- mouse model.ResultsReduced ADP sensitivity is associated with increases in mitochondrial ROS production in aged (62%) and Sod1 -/- (33%) mice. The maximal capacity to produce ROS does not increase with age, and there is no effect of age on ADP sensitivity for OCR in mouse gastrocnemii. Denervation does not induce ADP insensitivity for either ROS generation or OCR. Treatment of Sod1 -/- mice with SS-31 increases ADP sensitivity for both OCR and ROS, decreases maximal ROS production (~40%), and improves resistance to muscle fatigue.ConclusionsAdenosine diphosphate sensitivity for ROS production decreases in aged mouse gastrocnemius muscle fibres, although aged mice do not exhibit a difference in OCR. Denervation does not induce ADP insensitivity; however, insensitivity to ADP is induced in a model of oxidative stress. ADP insensitivity could contribute to muscle fatigue, and SS-31 may be the first drug capable of targeting this aging phenotype.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In Sod1-/- mice, SS‑31 increased ADP sensitivity for oxygen consumption in gastrocnemius muscle fibres.

    In plain wordsIn mice with high oxidative stress, SS‑31 made muscle mitochondria respond better to ADP for oxygen use.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseADP sensitivity for oxygen consumption rate
    Study

    mousen: not reported in source

    Sod1-/- mice
    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment of Sod1 -/- mice with SS-31 increases ADP sensitivity for both OCR and ROS
    1 context sentence
    Summary · context
    Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the Sod1 -/- mouse model.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In Sod1-/- mice, SS‑31 increased ADP sensitivity for reactive oxygen species production in gastrocnemius muscle fibres.

    In plain wordsIn mice with high oxidative stress, SS‑31 made muscle mitochondria respond better to ADP for reactive oxygen species control.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseADP sensitivity for ROS production
    Study

    mousen: not reported in source

    Sod1-/- mice
    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment of Sod1 -/- mice with SS-31 increases ADP sensitivity for both OCR and ROS
    1 context sentence
    Summary · context
    Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the Sod1 -/- mouse model.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In Sod1-/- mice, SS‑31 decreased maximal reactive oxygen species production in muscle by about 40%.

    In plain wordsIn mice with high oxidative stress, SS‑31 lowered the top level of reactive oxygen species made in muscle.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseMaximal ROS production
    Study

    mousen: not reported in source

    Sod1-/- mice
    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Measurements

    Maximal ROS production reduction
    ≈ 40%
    Sod1-/- mice with SS-31

    Source sentences

    Summary
    decreases maximal ROS production (~40%), and improves resistance to muscle fatigue.
    1 context sentence
    Summary · context
    Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the Sod1 -/- mouse model.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In Sod1-/- mice, SS‑31 improved resistance to muscle fatigue.

    In plain wordsIn mice with high oxidative stress, SS‑31 improved muscle resistance to fatigue.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseResistance to muscle fatigue
    Study

    mousen: not reported in source

    Sod1-/- mice
    Outcome group
    Exercise and physical function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    improves resistance to muscle fatigue.
    1 context sentence
    Summary · context
    Further, we asked whether the mitochondrial-targeted peptide SS-31 can modulate ADP insensitivity and contractile function in the Sod1 -/- mouse model.

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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