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Genome-wide CRISPR/Cas9 deletion screen defines mitochondrial gene essentiality and identifies routes for tumour cell viability in hypoxia
- Source :
- Communications Biology, Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021)
- Publication Year :
- 2021
- Publisher :
- Apollo - University of Cambridge Repository, 2021.
-
Abstract
- Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): FP7/2007-2013<br />Mitochondria 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.
- Subjects :
- Cancer microenvironment
0301 basic medicine
Mitochondrial DNA
82/29
QH301-705.5
45/41
Medicine (miscellaneous)
Biology
Mitochondrion
631/67/2327
Genome informatics
Genome
Oxidative Phosphorylation
General Biochemistry, Genetics and Molecular Biology
45/29
38/43
82/80
03 medical and health sciences
0302 clinical medicine
Neoplasms
Tumor Cells, Cultured
Humans
CRISPR
Viability assay
Biology (General)
Hypoxia
Gene
13/89
Cell Proliferation
96/106
Cas9
Cell growth
article
45/77
Cancer metabolism
Mitochondria
Cell biology
Genes, Mitochondrial
030104 developmental biology
030220 oncology & carcinogenesis
Genome, Mitochondrial
631/114/2785
38/39
CRISPR-Cas Systems
General Agricultural and Biological Sciences
82/1
Glycolysis
631/67/327
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Communications Biology, Communications Biology, Vol 4, Iss 1, Pp 1-12 (2021)
- Accession number :
- edsair.doi.dedup.....e823e6e04fe585b3faae4bcac5aa0908
- Full Text :
- https://doi.org/10.17863/cam.70257