The Contextual Essentiality of Mitochondrial Genes in Cancer.
Thomas, Luke W
Front Cell Dev Biol
Frontiers Media SA
MetadataShow full item record
Thomas, L. W., & Ashcroft, M. (2021). The Contextual Essentiality of Mitochondrial Genes in Cancer.. Front Cell Dev Biol, 9 695351. https://doi.org/10.3389/fcell.2021.695351
Mitochondria are key organelles in eukaryotic evolution that perform crucial roles as metabolic and cellular signaling hubs. Mitochondrial function and dysfunction are associated with a range of diseases, including cancer. Mitochondria support cancer cell proliferation through biosynthetic reactions and their role in signaling, and can also promote tumorigenesis via processes such as the production of reactive oxygen species (ROS). The advent of (nuclear) genome-wide CRISPR-Cas9 deletion screens has provided gene-level resolution of the requirement of nuclear-encoded mitochondrial genes (NEMGs) for cancer cell viability (essentiality). More recently, it has become apparent that the essentiality of NEMGs is highly dependent on the cancer cell context. In particular, key tumor microenvironmental factors such as hypoxia, and changes in nutrient (e.g., glucose) availability, significantly influence the essentiality of NEMGs. In this mini-review we will discuss recent advances in our understanding of the contribution of NEMGs to cancer from CRISPR-Cas9 deletion screens, and discuss emerging concepts surrounding the context-dependent nature of mitochondrial gene essentiality.
essentiality, metabolism, mitochondria, signaling, viability
LWT was funded by the Wellcome Trust (grant RG93172), Isaac Newton Trust [grant 21.07(b)] and Cancer Research UK Cambridge Cancer Centre funding awarded to MA.
External DOI: https://doi.org/10.3389/fcell.2021.695351
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329799
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
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