Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy

The Journal of Clinical Investigation
Yueming ZhuDavid Gius

Abstract

Mammalian cells use a complex network of redox-dependent processes necessary to maintain cellular integrity during oxidative metabolism, as well as to protect against and/or adapt to stress. The disruption of these redox-dependent processes, including those in the mitochondria, creates a cellular environment permissive for progression to a malignant phenotype and the development of resistance to commonly used anticancer agents. An extension of this paradigm is that when these mitochondrial functions are altered by the events leading to transformation and ensuing downstream metabolic processes, they can be used as molecular biomarkers or targets in the development of new therapeutic interventions to selectively kill and/or sensitize cancer versus normal cells. In this Review we propose that mitochondrial oxidative metabolism is altered in tumor cells, and the central theme of this dysregulation is electron transport chain activity, folate metabolism, NADH/NADPH metabolism, thiol-mediated detoxification pathways, and redox-active metal ion metabolism. It is proposed that specific subgroups of human malignancies display distinct mitochondrial transformative and/or tumor signatures that may benefit from agents that target these pat...Continue Reading

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Citations

May 7, 2019·Expert Review of Proteomics·Zhefeng Xiao, Zhuchu Chen
Jul 11, 2019·Cancers·Vinee PurohitCostas A Lyssiotis
Jun 11, 2019·Frontiers in Physiology·Jie CuiHongyi Zhang
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Mar 4, 2020·International Journal of Oncology·Romina Gabriela ArmandoDaniel Eduardo Gomez
Jun 25, 2020·International Journal of Molecular Sciences·Jean NakhleMarie-Luce Vignais
Jul 31, 2020·Frontiers of Medicine·Ke Sheng
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Jun 4, 2019·Seminars in Cell & Developmental Biology·Fabio FerroLucie Brisson

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Methods Mentioned

BETA
acetylation

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