ArticleCancer discovery2023
Effectors Enabling Adaptation to Mitochondrial Complex I Loss in Hürthle Cell Carcinoma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Photo-induced electron pumping meets nanozyme cascade: Triggering multimodal cell death for potent triple-negative breast cancer immunotherapy.Materials today. Bio · 2026Article
- GutiMeta · 2026Article
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.Science advances · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.bioRxiv : the preprint server for biology · 2025Article
- The Role of Mitochondrial Complexes in Liver Diseases.Journal of clinical and translational hepatology · 2025Review
- Article
- Historical rise of cancer and dietary linoleic acid: Mechanisms and therapeutic strategies.World journal of clinical oncology · 2025Review
- Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.Nature neuroscience · 2025Article
- CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma.Cancer discovery · 2025Article
- BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer.Life metabolism · 2024Article
- Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks.Oncogene · 2024Article
- Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.Nature communications · 2024Article
- Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.Molecular cell · 2024Article
- Forward Genetic Screens Identify Mechanisms of Resistance to Small-Molecule Lactate Dehydrogenase Inhibitors.ACS chemical biology · 2024Article
- Modulating gene expression as a strategy to investigate thyroid cancer biology.Archives of endocrinology and metabolism · 2024Review
- Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity. SIGNIFICANCE: HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.