{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331349"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Complex I Drives Glutamine-Dependent TCA Cycle to Support Viability of MYChigh Breast Cancer Cells","description":"In many cancers, stably elevated MYC levels drive persistent and concerted activation of cell growth promoting anabolic programs and cell cycle in ways distinct from normal cells. Therefore, synthetic-lethal targeting of MYC-reprogrammed pathways offers selective strategies against MYChigh tumors. This study identifies enhanced mitochondrial respiration as a hallmark of MYC overexpressing cancer cells. Mitochondrial respiration sustains TCA cycle by regenerating NAD+ through complex I-mediated oxidation of NADH. Metabolic carbon tracing analysis reveals that MYC shifts TCA cycle carbon source from glucose to glutamine. Inhibition of the glutamine-fueled TCA cycle using NAD+-depleting complex I inhibitors promotes MYC-dependent synthetic lethality in breast cancer cells. In mouse models of MYChigh tumors, persistent inhibition of tumor growth is achieved through combined inhibition of complex I and glutaminolysis. Altogether, the high respiration rate observed in MYChigh cells supports a glutamine carbon-enriched TCA cycle rendering MYChigh tumors selectively vulnerable to inhibitors of mitochondrial respiration and glutaminolysis. This deposition specifically contains the RNA-sequencing data generated from the breast cancer cell lines described in the study.","dates":{"publication":"2026/05/19"},"accession":"GSE331349","cross_references":{"GSM":["GSM9744449","GSM9744448","GSM9744469","GSM9744447","GSM9744464","GSM9744486","GSM9744485","GSM9744463","GSM9744484","GSM9744462","GSM9744461","GSM9744483","GSM9744446","GSM9744468","GSM9744467","GSM9744445","GSM9744466","GSM9744444","GSM9744488","GSM9744487","GSM9744465","GSM9744482","GSM9744460","GSM9744481","GSM9744480","GSM9744459","GSM9744458","GSM9744475","GSM9744453","GSM9744452","GSM9744474","GSM9744473","GSM9744451","GSM9744472","GSM9744450","GSM9744479","GSM9744457","GSM9744478","GSM9744456","GSM9744455","GSM9744477","GSM9744476","GSM9744454","GSM9744471","GSM9744470"],"GPL":["18573"],"GSE":["331349"],"taxon":["Homo sapiens"]}}