{
  "abstract": "Ferroptosis, mitochondrial stress and redox imbalance are increasingly recognised as interconnected determinants of therapeutic efficacy, drug resistance and organ toxicity. Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and impaired antioxidant defences, with relevance to cancer, cardiovascular disease, inflammatory disorders, ischaemia-reperfusion injury and drug-induced tissue damage. This Perspective reframes the ferroptosis-mitochondrial stress-redox axis as a unified pharmacological-toxicological platform rather than an isolated therapeutic target, resolving its mechanisms to individual electron transport chain complexes, membrane phospholipid species and downstream immunological consequences. Beyond the conventional GPX4-system Xc ⁻ NRF2 framework, we incorporate dihydroorotate dehydrogenase (DHODH), GCH1-BH4 signalling, NCOA4-mediated ferritinophagy and p53-dependent regulation of ferroptosis sensitivity. We further define how complex I- and III-derived superoxide, compartmentalised inner-membrane lipid pools and ACSL4/LPCAT3-directed phospholipid remodelling shape organ-specific vulnerability. Because ferroptotic cells release damage-associated molecular patterns whose effects depend on cell death kinetics, immunomodulation is considered a distinct therapeutic opportunity and safety consideration. To consolidate these interacting mechanisms into a single, comprehensible reference, we present an integrated molecular pathway diagram that maps oxidative-stress chemistry, compartment-resolved mitochondrial involvement, lipid-substrate specificity, cell-death execution and kinetics-dependent immunological crosstalk onto their corresponding pharmacological entry points. We propose a tiered biomarker framework, a p53-and biomarker-guided patient stratification strategy, a chemically stratified therapeutic map distinguishing repurposed drugs from experimental compounds, and a conceptual pharmacokinetic-pharmacodynamic framework linking therapeutic and toxic exposure windows. Future research should prioritise biomarker validation, complex-specific mitochondrial functional assays, lipidomic profiling, organ-specific toxicology, tumour-selective delivery systems and pharmacokinetic-pharmacodynamic integration to advance safer, more precise ferroptosis-based therapeutics.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Research, Publication and Extension, Kampala International University",
    "Department of Anatomy, Faculty of Biomedical Sciences, Kampala International University",
    "Department of Human Anatomy, State University of Medical and Applied Sciences"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Okechukwu Paul-Chima Ugwu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chinyere Nneoma Ugwu"
    },
    {
      "affs": [
        1
      ],
      "name": "Godson Emeka Anyanwu"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariam Basajja"
    },
    {
      "affs": [
        2
      ],
      "name": "Maryann Chiamaka Ebuoh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/96k9w3k8d6nqq.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1890015",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735567/",
  "id": "96k9w3k8d6nqq",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1890015/full",
  "language": "en",
  "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": [
    [
      "heading",
      "Perspective"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7223185712",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1890015/pdf",
  "pmcid": "PMC13735567",
  "pmid": "42991258",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/96k9w3k8d6nqq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1890015",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1890015/full"
    },
    {
      "first_seen": "2026-11-09T12:21:13Z",
      "native_id": "PMC13735567",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1890015"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Ferroptosis, mitochondrial stress and redox imbalance: a pharmacological-toxicological biochemistry framework for precision drug therapeutics",
  "title_text": "Ferroptosis, mitochondrial stress and redox imbalance: a pharmacological-toxicological biochemistry framework for precision drug therapeutics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:13Z",
  "url": "https://research.draconitic.com/paper/96k9w3k8d6nqq",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}