{
  "abstract": "Mitochondrial dysfunction is a recurring mechanism in neuronal vulnerability and in the toxicity of several neuroactive compounds, yet lesions at different respiratory-chain nodes are commonly treated as a single bioenergetic defect. Whether pharmacological perturbation at distinct nodes leaves neuronal cells in distinguishable metabolic states has not been examined across all five complexes in one system. Undifferentiated SH-SY5Y human neuroblastoma cells were exposed to five compounds selected as pharmacological perturbagens nominally directed at Complexes I–V: MPTP, 3-nitropropionic acid (3-NP), antimycin A, sodium azide and oligomycin, each titrated to approximately 80% viability (24 h, except 3-NP at 12 h). Inhibitors were then removed, and cells were labelled for 24 h with [U-13C6]glucose. Positional 13C-NMR was combined with pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) enzyme-capacity assays in parallel extracts from the same biological replicates (n = 3 per group). The design is a single-factor, six-level layout in which five exposures share one vehicle control; labelling data were log2-transformed and analysed by one-way ANOVA with Dunnett many-to-one contrasts (error df = 12), with Hedges’ g and 95% confidence intervals, and group structure was tested by permutational multivariate analysis of variance (PERMANOVA). PERMANOVA demonstrated a significant overall effect of exposure group on the multivariate labelling matrix (pseudo-F = 18.77, p = 0.0001, 9999 permutations), and principal component analysis of the seven complete-case metabolites showed visually distinct group structure (PC1 65.9%, PC2 19.3%; 85.3% cumulative). Oligomycin produced the most distinct positional phenotype, preserving the PDH-associated glutamate C4 readout (107.2% of control, p = 0.971) while nearly doubling the PC-associated glutamate C3 readout (197.7%, p = 0.004; Hedges’ g = 17.8, 95% CI 5.3–30.2), concordant with PC capacity at approximately 138% and PDH capacity at approximately 60% of control. Azide produced the strongest reduction in glutamate C4 labelling (31.9%, p < 0.001; g = −8.3); antimycin A produced the broadest suppression of labelling; 3-NP produced accumulation of 13C-labelled succinate that was undetectable in the control. MPTP gave the weakest phenotype, with most of its individual comparisons not surviving the shared-control analysis. Exposure to compounds directed at different respiratory nodes leaves neuronal cells in non-equivalent post-exposure 13C-labelling states that positional 13C-NMR resolves. Because tracing followed washout, because the compounds are not fully selective and because the enzyme assays report capacity rather than flux, these are compound-defined post-exposure metabolic states and not measurements of complex-specific flux.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Advanced Metabolomics and Proteomics Research, Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA",
    "Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34450, Turkey",
    "Department of Biochemistry and Molecular Biology, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34450, Turkey",
    "Acibadem Labmed Clinical Laboratories, Istanbul 34450, Turkey"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hong Li"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Ahmet Tarık Baykal",
      "orcid": "0000-0002-8814-7351"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/29tt41jcm6wcy.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209160",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705396/?tool=EBI",
  "id": "29tt41jcm6wcy",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9160",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7221992851",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705396/pdf/?tool=EBI",
  "pmcid": "PMC13705396",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/29tt41jcm6wcy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209160",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9160"
    },
    {
      "first_seen": "2026-10-30T12:21:34Z",
      "native_id": "PMC:PMC13705396",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705396"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Distinct Post-Exposure Metabolic States Following Pharmacological Perturbation of Mitochondrial Respiratory Complexes I–V in SH-SY5Y Cells: A Positional 13C-NMR Study",
  "title_text": "Distinct Post-Exposure Metabolic States Following Pharmacological Perturbation of Mitochondrial Respiratory Complexes I–V in SH-SY5Y Cells: A Positional 13C-NMR Study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:34Z",
  "url": "https://research.draconitic.com/paper/29tt41jcm6wcy",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}