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Review
. 2023 Oct 25:14:1243613.
doi: 10.3389/fphar.2023.1243613. eCollection 2023.

The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis

Yi Yang  1 , Yahui An  1 , Mingli Ren  1 , Haijiao Wang  1 , Jing Bai  1 , Wenli Du  1 , Dezhi Kong  2
Affiliations
Review

The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis

Yi Yang et al. Front Pharmacol. .

Abstract

The tumor microenvironment affects the structure and metabolic function of mitochondria in tumor cells. This process involves changes in metabolic activity, an increase in the amount of reactive oxygen species (ROS) in tumor cells compared to normal cells, the production of more intracellular free radicals, and the activation of oxidative pathways. From a practical perspective, it is advantageous to develop drugs that target mitochondria for the treatment of malignant tumors. Such drugs can enhance the selectivity of treatments for specific cell groups, minimize toxic effects on normal tissues, and improve combinational treatments. Mitochondrial targeting agents typically rely on small molecule medications (such as synthetic small molecules agents, active ingredients of plants, mitochondrial inhibitors or autophagy inhibitors, and others), modified mitochondrial delivery system agents (such as lipophilic cation modification or combining other molecules to form targeted mitochondrial agents), and a few mitochondrial complex inhibitors. This article will review these compounds in three main areas: oxidative phosphorylation (OXPHOS), changes in ROS levels, and endogenous oxidative and apoptotic processes.

Keywords: electron transport chain (ETC); mechanism; mitocans; mitochondria targeting drug; oxidative phoshorylation; reactive oxygen species.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Summary of the mechanism and related pathways of mitochondrial targeting agents.
FIGURE 2
FIGURE 2
Summary of the mechanism and related apoptosis pathways of mitochondrial targeting agents.
See this image and copyright information in PMC

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Grants and funding

Support was provided by the Hebei Natural Science Foundation (No. H202206444; Shijiazhuang, China).

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