ROS systems are a new integrated network for sensing homeostasis and alarming stresses in organelle metabolic processes

Abstract

Reactive oxygen species (ROS) are critical for the progression of cardiovascular diseases, inflammations and tumors. However, the mechanisms of how ROS sense metabolic stress, regulate metabolic pathways and initiate proliferation, inflammation and cell death responses remain poorly characterized. In this analytic review, we concluded that: 1) Based on different features and functions, eleven types of ROS can be classified into seven functional groups: metabolic stress-sensing, chemical connecting, organelle communication, stress branch-out, inflammasome-activating, dual functions and triple functions ROS. 2) Among the ROS generation systems, mitochondria consume the most amount of oxygen; and nine types of ROS are generated; thus, mitochondrial ROS systems serve as the central hub for connecting ROS with inflammasome activation, trained immunity and immunometabolic pathways. 3) Increased nuclear ROS production significantly promotes cell death in comparison to that in other organelles. Nuclear ROS systems serve as a convergent hub and decision-makers to connect unbearable and alarming metabolic stresses to inflammation and cell death. 4) Balanced ROS levels indicate physiological homeostasis of various metabolic processes in subcellular organelles and cytosol, while imbalanced ROS levels present alarms for pathological organelle stresses in metabolic processes. Based on these analyses, we propose a working model that ROS systems are a new integrated network for sensing homeostasis and alarming stress in metabolic processes in various subcellular organelles. Our model provides novel insights on the roles of the ROS systems in bridging metabolic stress to inflammation, cell death and tumorigenesis; and provide novel therapeutic targets for treating those diseases. (Word count: 246).

Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer

“…Cellular aerobic reactions continuously produce reactive oxygen species (ROS) called reduced oxygen compounds or by-products that perform crucial function [ 1 ]. Dysregulation of aerobic metabolism at cellular levels causes elevation of ROS that damages cellular macromolecular components responsible for regulation of signaling and differentiation processes related to cell damage and death [ 2 ].…”

Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance

“…It is now recognized that inflammation induced by pathogen-associated molecular patterns (PAMPs) [ 26 ] and danger/conditional danger-associated molecular patterns (conditional DAMPs) [ 27 ] is an essential mechanism of innate immune response [ 28 ]. Classical danger/damage-associated molecular patterns (DAMPs) bind to various innate immune pattern receptors such as Toll-like receptors and NOD-like receptors [ 29 – 31 ], whereas pathologically elevated endogenous metabolite-derived DAMPs that bind to their own receptors are termed as conditional DAMPs as we proposed in 2016 [ 27 , 32 ]. We recently proposed that vascular endothelial cells are innate immune cells [ 30 , 33 ].…”

Innate-adaptive immunity interplay and redox regulation in immune response

“…The activity of NOX is dependent on subunit interaction [ 97 ]. In response to danger signals, including PAMP, DAMP and MADS, plasma membrane located NOX1/2 are activated [ 98 ]. Activated NOX1/2 produce and release O 2 •- directly into the extracellular spaces which are dismutated into H 2 O 2 by superoxide dismutase (SOD) 3.…”

“…Reodx regulation is implicated in modulating innate and adaptive immunity and pathophysilology of many diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, cancer, and neurodegenerative diseases [ 98 , 109 ]. Increasing efforts have been made to study the effects of antioxidants on the prevention and treatment of these diseases [ 110 ].…”