Redox homeostasis is attained by the cautious regulation of both reactive oxygen species (ROS) formation and removal from the body system. A shift in ROS balance promotes oxidative injury and tumour development by inflicting damage to DNA and inducing inconsistencies in the genome. The sources of endogenous ROS in a cell include mETC, NOX, LOX, cytochrome P450 and XO. The exogenous risk factors of ROS are pollutants, chemicals/drugs, radiation and heavy metals. Oxidative phosphorylation in the mitochondria produces ROS with unpaired electrons. Superoxide anion is the major ROS produced in the human mitochondria. Bulk of the ROS generation in the mitochondria occurs at the electron transport chain as derivatives of respiration. Cancer cells sustain ROS production by suppressing the antioxidant-generation system. Balance between ROS production and subsequent detoxification is regulated by scavenging enzymes and antioxidant agents. Failure in sirtuin-3 (SIRT3), ATM and p53 activities elevates the intracellular levels of ROS. PKCα induces the expression of NOX (DUOX) during cancer development and the consequent increase in ROS production. The PI3K/AKT signalling pathway activates NOX with consequent ROS production and subsequent induction of instability in the genome, leading to cancer. In conclusion, the interruption of the redox pathways that regulate ROS and its redox signalling activities affects cell physiology and can ultimately result in abnormal signalling, uncontrolled oxidative impairment and tumorigenesis.
Part of the book: Homeostasis