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Mitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression

Journal

ANTIOXIDANTS
Volume 10, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/antiox10111838

Keywords

mitochondrial redox metabolism; ROS signaling; tumor development; metastasis; distant colonization

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Mitochondrial redox metabolism plays a crucial role in cancer progression, regulating metabolic adaptation and maintaining cellular redox homeostasis. The flexibility of mitochondrial metabolism is essential for cancer cells to adapt to new environments and overcome metabolic limitations, especially during different stages of metastasis.
Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells' progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment.

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