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The Contextual Essentiality of Mitochondrial Genes in Cancer.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Thomas, Luke W 

Abstract

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.

Description

Keywords

essentiality, metabolism, mitochondria, signaling, viability

Journal Title

Front Cell Dev Biol

Conference Name

Journal ISSN

2296-634X
2296-634X

Volume Title

9

Publisher

Frontiers Media SA
Sponsorship
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.