Deconvoluting the role of reactive oxygen species and autophagy in human diseases

Abstract

Reactive oxygen species (ROS), chemically reactive molecules containing oxygen, can form as a natural byproduct of the normal metabolism of oxygen and also have their crucial roles in cell homeostasis. Of note, the major intracellular sources including mitochondria, endoplasmic reticulum (ER), peroxisomes and the NADPH oxidase (NOX) complex have been identified in cell membranes to produce ROS. Interestingly, autophagy, an evolutionarily conserved lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles, has recently been well-characterized to be regulated by different types of ROS. Accumulating evidence has demonstrated that ROS-modulated autophagy has numerous links to a number of pathological processes, including cancer, ageing, neurodegenerative diseases, type-II diabetes, cardiovascular diseases, muscular disorders, hepatic encephalopathy and immunity diseases. In this review, we focus on summarizing the molecular mechanisms of ROS-regulated autophagy and their relevance to diverse diseases, which would shed new light on more ROS modulators as potential therapeutic drugs for fighting human diseases.

Keywords: (1)O(2); 2-Deoxy-D-glucose; 2-ME; 2-methoxyestradiol; 2DG; 3-nitropropionic acid; 3NP; ASK1; ATM; Ageing; Atg; Autophagy; BNIP3; Bax-interacting factor-1; Bcl-2/E1B interacting protein 3; Bif-1; Cancer; Cardiovascular diseases; Class III phosphatidylinositol 3-kinase; CoQ; Cu(+); EDD; ER; ER-β; ERK; FIP200; Fe(2+); Free radicals; H(2)O(2); HE; Hepatic encephalopathy; Immunity diseases; JNK; LAMP1 and LAMP2; MAPK; Muscular disorders; NADPH oxidase; NO; NOX; Neurodegenerative diseases; O(2)(–•); OH(–); PI3KCIII; PtdIns; ROS; Reactive oxygen species; SOD; Type-II diabetes; ULK1/2; UV irradiation resistance-associated gene; UVRAG; Unc51-Like Kinase 1/2; XO; apoptosis signal-regulating kinase 1; ataxia-telangiectasia mutated; autophagy-related gene; c-Jun N-terminal kinase; coenzyme Q; cyto. c; cytochrome c; endoplasmic reticulum; endothelium-dependent dilatation; estrogen receptor beta; extracellular regulated kinase; focal adhesion kinase family interaction protein of 200-kDa; hepatic encephalopathy; hydrogen peroxide; hydroxyl radical; lysosomal-associated proteins 1 and 2; mETC; mitochondrial electron-transport chain; mitogen-activated protein kinase; nitric oxide; phosphatidylinositol; reactive oxygen species; reduced copper; reduced iron; singlet oxygen; superoxide; superoxide dismutase; xanthine oxidase..