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dc.contributor.authorThomas, Luke W
dc.contributor.authorEsposito, Cinzia
dc.contributor.authorMorgan, Rachel E
dc.contributor.authorPrice, Stacey
dc.contributor.authorYoung, Jamie
dc.contributor.authorWilliams, Steven P
dc.contributor.authorMaddalena, Lucas A
dc.contributor.authorMcDermott, Ultan
dc.contributor.authorAshcroft, Margaret
dc.description.abstractMitochondria are typically essential for the viability of eukaryotic cells, and utilize oxygen and nutrients (e.g. glucose) to perform key metabolic functions that maintain energetic homeostasis and support proliferation. Here we provide a comprehensive functional annotation of mitochondrial genes that are essential for the viability of a large panel (625) of tumour cell lines. We perform genome-wide CRISPR/Cas9 deletion screening in normoxia-glucose, hypoxia-glucose and normoxia-galactose conditions, and identify both unique and overlapping genes whose loss influences tumour cell viability under these different metabolic conditions. We discover that loss of certain oxidative phosphorylation (OXPHOS) genes (e.g. SDHC) improves tumour cell growth in hypoxia-glucose, but reduces growth in normoxia, indicating a metabolic switch in OXPHOS gene function. Moreover, compared to normoxia-glucose, loss of genes involved in energy-consuming processes that are energetically demanding, such as translation and actin polymerization, improve cell viability under both hypoxia-glucose and normoxia-galactose. Collectively, our study defines mitochondrial gene essentiality in tumour cells, highlighting that essentiality is dependent on the metabolic environment, and identifies routes for regulating tumour cell viability in hypoxia.
dc.rightsAttribution 4.0 International
dc.sourceessn: 2399-3642
dc.sourcenlmid: 101719179
dc.titleGenome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia.
prism.publicationNameCommunications biology
dc.contributor.orcidThomas, Luke W [0000-0002-2246-0361]
dc.contributor.orcidAshcroft, Margaret [0000-0002-0066-3707]
pubs.funder-project-idWellcome Trust (RG93172)
pubs.funder-project-idCUH | Addenbrooke's Charitable Trust, Cambridge University Hospitals (Addenbrooke's Charitable Trust, Cambridge University Hospitals NHS Foundation Trust) (900187)
pubs.funder-project-idMedical Research Council (MR/K002201/2)
pubs.funder-project-idEuropean Research Council (FP7/2007-2013, 319661)
pubs.funder-project-idCancer Research UK (RG91141, C7358/A19442)

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International