Metabolomic and gene networks approaches reveal the role of mitochondrial membrane proteins in

Biochim Biophys Acta Mol Cell Biol Lipids · 2025 · Mixed · Low evidence

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MixedLow evidencePaper 286

Study snapshot

PublicationBiochim Biophys Acta Mol Cell Biol Lipids · 2025

Study typein_vitro

Reported directionMixed

Evidence ratingLow

Abstract

Metabolomic and gene networks approaches reveal the role of mitochondrial membrane proteins in response of human melanoma cells to THz radiation Butikova EA, Basov NV, Rogachev AD, Gaisler EV, Ivanisenko VA, Demenkov PS, Makarova AA, Ivanisenko TV, Razumov IA, Kolomeyets DA, Cheresiz SV, Solovieva OI, Larionov KP, Sotnikova YS, Patrushev YV, Kolchanov NA, Pokrovsky AG, Vinokurov NA, Kanygin VV, Popik VM, Shevchenko OA. Metabolomic and gene networks approaches reveal the role of mitochondrial membrane proteins in response of human melanoma cells to THz radiation. Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jan 20:159595. doi: 10.1016/j.bbalip.2025.159595. This paper presents a study on the biological effects of terahertz irradiation with a frequency of 2.3 THz and a power of 0.056 W/cm2 on SK-MEL-28 cells, using targeted metabolomic screening by liquid chromatography and tandem mass spectrometry (LC-MS/MS) and gene network analysis. Highlights • THz radiation exposure induced significant changes in the levels of 40 metabolites, especially those related to purine and pyrimidine pathways. Lipids, such as ceramides and phosphatidylcholines, were also affected by this exposure. • Gene network reconstruction identified mitochondrial membrane proteins, including components of the respiratory chain complex, ATP synthase, and lipid rafts, as key regulators of the enzymes involved in biosynthesis and degradation of the significantly altered metabolites. • THz radiation induces reversible disruption of lipid raft macromolecular structure, altering mitochondrial molecule transport while maintaining protein integrity. • Importantly, the metabolic effects observed were specific to THz radiation and were not due to heating, as evidenced by the distinct responses in control cells exposed to infrared radiation. Abstract Terahertz (THz) radiation has gained attention due to technological advancements, but its biological effects remain unclear. We investigated the impact of 2.3 THz radiation on SK-MEL-28 cells using metabolomic and gene network analysis. Forty metabolites, primarily related to purine, pyrimidine synthesis and breakdown pathways, were significantly altered post-irradiation. Lipids, such as ceramides and phosphatidylcholines, were also affected. Gene network reconstruction and analysis identified key regulators of the enzymes involved in biosynthesis and degradation of significantly altered metabolites. Mitochondrial membrane components, such as the respiratory chain complex, the proton-transporting ATP synthase complex, and components of lipid rafts, reacted to THz radiation. We propose that THz radiation induces reversible disruption of the lipid raft macromolecular structure, thereby altering mitochondrial molecule transport while maintaining protein integrity, which explains the high cell survival rate. Our findings enhance the understanding of THz biological effects and emphasize the role of membrane components in the cellular response to THz radiation. sciencedirect.com

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 typein_vitro

Effect directionmixed

PopulationHuman melanoma cell line SK-MEL-28

Sample sizeNot supplied

ExposureTHz · 2.3e+06 MHz

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Exposure of SK-MEL-28 cells to 2.3 THz radiation (0.056 W/cm2) was associated with significant changes in 40 metabolites, particularly in purine/pyrimidine pathways, and changes in lipids including ceramides and phosphatidylcholines. Gene network analysis implicated mitochondrial membrane proteins (respiratory chain complex, ATP synthase, lipid raft components) as key regulators, and the authors report reversible disruption of lipid raft structure with high cell survival; effects were described as distinct from infrared controls and not attributable to heating.

Outcomes measured

Targeted metabolomic changes (LC-MS/MS)
Alterations in purine and pyrimidine pathway metabolites
Lipid metabolite changes (ceramides, phosphatidylcholines)
Gene network reconstruction identifying regulators/mitochondrial membrane components
Lipid raft macromolecular structure disruption (reversible)
Mitochondrial molecule transport alteration
Cell survival rate (reported as high)
Comparison with infrared radiation controls to assess heating contribution

Limitations

Exposure duration not reported in the provided abstract/metadata
Sample size/number of replicates not reported
In vitro model (single human melanoma cell line) limits generalizability to humans
Mechanistic conclusions are partly framed as a proposal ("We propose...") rather than directly demonstrated in the abstract

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": "THz",
    "source": null,
    "frequency_mhz": 2300000,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Human melanoma cell line SK-MEL-28",
  "sample_size": null,
  "outcomes": [
    "Targeted metabolomic changes (LC-MS/MS)",
    "Alterations in purine and pyrimidine pathway metabolites",
    "Lipid metabolite changes (ceramides, phosphatidylcholines)",
    "Gene network reconstruction identifying regulators/mitochondrial membrane components",
    "Lipid raft macromolecular structure disruption (reversible)",
    "Mitochondrial molecule transport alteration",
    "Cell survival rate (reported as high)",
    "Comparison with infrared radiation controls to assess heating contribution"
  ],
  "main_findings": "Exposure of SK-MEL-28 cells to 2.3 THz radiation (0.056 W/cm2) was associated with significant changes in 40 metabolites, particularly in purine/pyrimidine pathways, and changes in lipids including ceramides and phosphatidylcholines. Gene network analysis implicated mitochondrial membrane proteins (respiratory chain complex, ATP synthase, lipid raft components) as key regulators, and the authors report reversible disruption of lipid raft structure with high cell survival; effects were described as distinct from infrared controls and not attributable to heating.",
  "effect_direction": "mixed",
  "limitations": [
    "Exposure duration not reported in the provided abstract/metadata",
    "Sample size/number of replicates not reported",
    "In vitro model (single human melanoma cell line) limits generalizability to humans",
    "Mechanistic conclusions are partly framed as a proposal (\"We propose...\") rather than directly demonstrated in the abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "terahertz",
    "THz radiation",
    "2.3 THz",
    "SK-MEL-28",
    "human melanoma cells",
    "metabolomics",
    "LC-MS/MS",
    "gene network analysis",
    "mitochondria",
    "mitochondrial membrane proteins",
    "lipid rafts",
    "purine pathway",
    "pyrimidine pathway",
    "ceramides",
    "phosphatidylcholines",
    "non-thermal effects",
    "infrared control"
  ],
  "suggested_hubs": [
    {
      "slug": "terahertz-thz",
      "weight": 0.95,
      "reason": "Study explicitly examines biological effects of 2.3 THz radiation in cells."
    }
  ]
}

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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: 10.1016/j.bbalip.2025.159595
PubMed: Not supplied

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