Physiological Ca 2+ Transients Versus Pathological Steady-State Ca 2+ Elevation, Who Flips the ROS Coin in Skeletal Muscle Mitochondria

2020 · Unclear · Insufficient evidence

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UnclearInsufficient evidencePaper 1647

Study snapshot

Publicationmanual · 2020

Study typereview

Reported directionUnclear

Evidence ratingInsufficient

Abstract

Physiological Ca 2+ Transients Versus Pathological Steady-State Ca 2+ Elevation, Who Flips the ROS Coin in Skeletal Muscle Mitochondria Ang Li, Jianxun Yi, Xuejun Li, Jingsong Zhou. Physiological Ca 2+ Transients Versus Pathological Steady-State Ca 2+ Elevation, Who Flips the ROS Coin in Skeletal Muscle Mitochondria. Front Physiol. 2020 Oct 22;11:595800. doi: 10.3389/fphys.2020.595800. Abstract Mitochondria are both the primary provider of ATP and the pivotal regulator of cell death, which are essential for physiological muscle activities. Ca2+ plays a multifaceted role in mitochondrial function. During muscle contraction, Ca2+ influx into mitochondria activates multiple enzymes related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation, resulting in increased ATP synthesis to meet the energy demand. Pathophysiological conditions such as skeletal muscle denervation or unloading also lead to elevated Ca2+ levels inside mitochondria. However, the outcomes of this steady-state elevation of mitochondrial Ca2+ level include exacerbated reactive oxygen species (ROS) generation, sensitized opening of mitochondrial permeability transition pore (mPTP), induction of programmed cell death, and ultimately muscle atrophy. Previously, both acute and long-term endurance exercises have been reported to activate certain signaling pathways to counteract ROS production. Meanwhile, electrical stimulation is known to help prevent apoptosis and alleviate muscle atrophy in denervated animal models and patients with motor impairment. There are various mechanistic studies that focus on the excitation-transcription coupling framework to understand the beneficial role of exercise and electrical stimulation. Interestingly, a recent study has revealed an unexpected role of rapid mitochondrial Ca2+ transients in keeping mPTP at a closed state with reduced mitochondrial ROS production. This discovery motivated us to contribute this review article to inspire further discussion about the potential mechanisms underlying differential outcomes of physiological mitochondrial Ca2+ transients and pathological mitochondrial Ca2+ elevation in skeletal muscle ROS production. Open access paper: ncbi.nlm.nih.gov

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typereview

Effect directionunclear

PopulationNot supplied

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthInsufficientConfidence: 66% · Peer reviewed: yes

Main findings

The review contrasts physiological mitochondrial Ca2+ transients during muscle contraction (linked to activation of TCA/oxidative phosphorylation enzymes and increased ATP synthesis) with pathological steady-state mitochondrial Ca2+ elevation in conditions such as denervation/unloading (associated with increased ROS generation, sensitized mPTP opening, programmed cell death, and muscle atrophy). It also notes reports that endurance exercise can activate signaling pathways that counteract ROS production and that electrical stimulation can help prevent apoptosis and alleviate muscle atrophy in denervated models/patients; a recent study is described as suggesting rapid mitochondrial Ca2+ transients may help keep mPTP closed with reduced ROS production.

Outcomes measured

mitochondrial Ca2+ transients
steady-state mitochondrial Ca2+ elevation
reactive oxygen species (ROS) generation
mitochondrial permeability transition pore (mPTP) opening
programmed cell death/apoptosis
muscle atrophy
ATP synthesis/mitochondrial metabolism (TCA cycle, oxidative phosphorylation)

Limitations

Narrative review; no primary data presented in the abstract
No EMF/RF exposure parameters (frequency, intensity, SAR, duration) are provided for electrical stimulation
Specific study designs, populations, and effect sizes of cited studies are not described in the abstract

View raw extracted JSON

{
  "study_type": "review",
  "exposure": {
    "band": null,
    "source": "electrical stimulation",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": null,
  "sample_size": null,
  "outcomes": [
    "mitochondrial Ca2+ transients",
    "steady-state mitochondrial Ca2+ elevation",
    "reactive oxygen species (ROS) generation",
    "mitochondrial permeability transition pore (mPTP) opening",
    "programmed cell death/apoptosis",
    "muscle atrophy",
    "ATP synthesis/mitochondrial metabolism (TCA cycle, oxidative phosphorylation)"
  ],
  "main_findings": "The review contrasts physiological mitochondrial Ca2+ transients during muscle contraction (linked to activation of TCA/oxidative phosphorylation enzymes and increased ATP synthesis) with pathological steady-state mitochondrial Ca2+ elevation in conditions such as denervation/unloading (associated with increased ROS generation, sensitized mPTP opening, programmed cell death, and muscle atrophy). It also notes reports that endurance exercise can activate signaling pathways that counteract ROS production and that electrical stimulation can help prevent apoptosis and alleviate muscle atrophy in denervated models/patients; a recent study is described as suggesting rapid mitochondrial Ca2+ transients may help keep mPTP closed with reduced ROS production.",
  "effect_direction": "unclear",
  "limitations": [
    "Narrative review; no primary data presented in the abstract",
    "No EMF/RF exposure parameters (frequency, intensity, SAR, duration) are provided for electrical stimulation",
    "Specific study designs, populations, and effect sizes of cited studies are not described in the abstract"
  ],
  "evidence_strength": "insufficient",
  "confidence": 0.66,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "mitochondria",
    "skeletal muscle",
    "calcium (Ca2+)",
    "ROS",
    "mPTP",
    "apoptosis",
    "muscle atrophy",
    "exercise",
    "electrical stimulation"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.3389/fphys.2020.595800
PubMed: Not supplied

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