ROS systems are a new integrated network for sensing homeostasis and alarming stresses in organelle metabolic processes
Yu Sun,
Yifan Lu,
Jason Saredy,
Xianwei Wang,
Charles Drummer IV,
Ying Shao,
Fatma Saaoud,
Keman Xu,
Ming Liu,
William Y. Yang,
Xiaohua Jiang,
Hong Wang,
Xiaofeng Yang
Affiliations
Yu Sun
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Yifan Lu
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Jason Saredy
Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Xianwei Wang
Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Charles Drummer IV
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Ying Shao
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Fatma Saaoud
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Keman Xu
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
Ming Liu
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA
William Y. Yang
Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Xiaohua Jiang
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA; Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Hong Wang
Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA
Xiaofeng Yang
Centers for Cardiovascular Research and Inflammation, Translational and Clinical Lung Research, USA; Metabolic Disease Research and Cardiovascular Research and Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Corresponding author. Centers for Cardiovascular Research, Inflammation, Translational and Clinical Lung Research, Metabolic Disease Research and Thrombosis Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Stress, Philadelphia, PA 19140, USA.
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).
