title: Redox homeostasis protects mitochondria through accelerating ROS conversion to enhance hypoxia resistance in cancer cells.
abstract: Mitochondria are the powerhouses of eukaryotic cells and the main source of reactive oxygen species (ROS) in hypoxic cells, participating in regulating redox homeostasis. The mechanism of tumor hypoxia tolerance, especially the role of mitochondria in tumor hypoxia resistance remains largely unknown. This study aimed to explore the role of mitochondria in tumor hypoxia resistance. We observed that glycolysis in hypoxic cancer cells was up-regulated more rapidly, with far lesser attenuation in aerobic oxidation, thus contributing to a more stable ATP/ADP ratio. In hypoxia, cancer cells rapidly convert hypoxia-induced O(2˙)(-) into H2O2. H2O2 is further decomposed by a relatively stronger antioxidant system, causing ROS levels to increase lesser compared to normal cells. The moderate ROS leads to an appropriate degree of autophagy, eliminating the damaged mitochondria and offering nutrients to promote mitochondria fusion, thus protects mitochondria and improves hypoxia tolerance in cancer. The functional mitochondria could enable tumor cells to flexibly switch between glycolysis and oxidative phosphorylation to meet the different physiological requirements during the hypoxia/re-oxygenation cycling of tumor growth.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Pengying
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Kelei
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Wu
authors.affiliation: Cancer Research Institute of Fudan University Shanghai Cancer Center, Shanghai 200032, People's Republic of China.
authors.forename: Zhouluo
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Shi
mesh_terms: D000332:Aerobiosis; D045744:Cell Line, Tumor; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000072258:Tumor Hypoxia
chemical_list: D017382:Reactive Oxygen Species