Abstract
Mitochondria are very important intracellular organelles because they have various functions. They produce ATP, are involved in cell signaling and cell death, and are a major source of reactive oxygen species (ROS). Mitochondria have their own DNA (mtDNA) and mutation of mtDNA or change the mtDNA copy numbers leads to disease, cancer chemo/radioresistance and aging including longevity. In this review, we discuss the mtDNA mutation, mitochondrial disease, longevity, and importance of mitochondrial dysfunction in cancer first. In the later part, we particularly focus on the role in cancer resistance and the mitochondrial condition such as mtDNA copy number, mitochondrial membrane potential, ROS levels, and ATP production. We suggest a therapeutic strategy employing mitochondrial transplantation (mtTP) for treatment-resistant cancer.
Highlights
Accepted: 26 August 2021A major function of mitochondria is the production of Adenosine tri-phosphate (ATP)
We have demonstrated that mitochondria from a non-cancer cell line can be transplanted into cancer cell lines that lack Mitochondria have their own DNA (mtDNA) (ρ0 cells) [94]
It has been reported that ALOX expression was enhanced in clinically relevant radioresistant (CRR) cells, and overexpression of ALOX12 enhances reactive oxygen species (ROS) generation and amount of HNE, which is one of the lipid peroxidation by-products [116]. These results indicate that the CRR cells inhibit ferroptosis and show resistance from oxidative stress via decreasing mitochondrial function
Summary
A major function of mitochondria is the production of Adenosine tri-phosphate (ATP). Mitochondria use pyruvic acid in the cytoplasm to efficiently produce ATP via the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). Association of Mitochondrial DNA (mtDNA) Mutations in Several Diseases, Longevity, and Radioresistance. This mutation has been reported to increase mitochondrial ROS production [44] and radiosensitivity. It has been reported that an increase in mtDNA copy number was protective in cancer [67]. We previously showed that ρ0 cells are more sensitive to hydrogen peroxide (H2 O2 ), which is a well-characterized ROS [75] These findings indicate that there are relationships among mtDNA aging, cancer progression and treatment resistance. It has been reported that cancer cells produce ATP via glycolysis rather than OXPHOS even under aerobic conditions [80,81], which leads to low ∆Ψm, resulting in resistance to cell death [82].
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