Autophagy is a catabolic procedure for unnecessary or dysfunctional cytoplasmic contents by lysosomal degradation pathways. constituents and thus incurs cell death. Hence, the balance of autophagy-related stress adaptation and cell death is important to comprehend redox signalling-related pathogenesis. In this review, we attempt to provide an overview the basic mechanism and function of autophagy in the context of response to oxidative stress and redox signalling in pathology. strong class=”kwd-title” Keywords: autophagy, reactive oxygen species, oxidative stress 1. Introduction Autophagy (self-eating) was first introduced by Christian de Duve in 1963 as a lysosome-mediated disposal process [1]. Autophagy is a catabolic process that is essential for cellular homeostasis through the removal of cellular molecules, such as protein aggregates and Fasudil HCl tyrosianse inhibitor damaged organelles, via lysosomal digestion [2,3]. Principally, it regulates the balance between organelle biogenesis, protein synthesis and the clearance of cells [4], which is involved in cellular remodelling during development and differentiation [5]. Autophagy occurs under conditions of glucose or amino acid deprivation, oxidative stress, hypoxia and exposure to xenobiotics [6]. Autophagy has emerged as a critical mediator of pathological responses is associated with reactive oxygen species (ROS) in both cellular signalling and damage [7]. The autophagy has also been implicated in the progression of diabetes, cancer, cardiovascular, neurodegeneration, immune diseases and ageing [8,9,10,11,12,13]. Mitochondria are the major source of ROS within cells [14,15] and mitochondrial ROS (mROS) are generally produced as by-products of the bioenergetics during oxidative phosphorylation (OXPHOS) [16]. The ROS Fasudil HCl tyrosianse inhibitor are highly reactive metabolites of molecular oxygen (O2), including superoxide anion (O2?) and hydrogen peroxide (H2O2), which are formed by electron reductions of O2 [17]. In the presence of transition metal ions, the more reactive hydroxyl radical (OH) is usually produced [18]. ROS can act as signalling molecules at the physiological level, which contribute to various cellular processes, including proliferation, differentiation, programmed cell death, innate immunity, autophagy, redox signalling, calcium homeostasis, hypoxic stress responses and stem cell reprogramming [19,20,21,22,23,24,25]. Conversely, extra SCDGF-B oxidative stress causes damages to proteins and cellular components, which is usually implicated in various pathologies [26]. Physiological ROS induce autophagy to maintain the cellular homeostasis in different types of cells, whereas dysregulation of redox signalling can demoralise the autophagic activity, which results in a variety of diseases [27,28]. However, the underlying mechanism between autophagy and redox signalling remains to be further elucidated. In this review, we introduce recent studies on redox signalling in autophagy regulation. Furthermore, we discuss the effect of autophagy on mitochondrial function and relevance to chronic pathologies. 2. Molecular Mechanisms of Autophagy 2.1. Autophagic Machinary There are three major types of autophagy: (1) macro-autophagy, (2) micro-autophagy, and (3) chaperone-mediated autophagy (CMA) (Physique 1). Macro-autophagy is the most well-known form of autophagy. All types of autophagy promote degradation of damaged or functionally expired proteins and organelles in the cell. Open in a separate window Physique 1 Overview of the mammalian autophagy pathway. Macro-autophagy encapsulates the cytoplasmic cargo by a delimiting membrane, which forms an autophagosome, which finally fuses with lysosome for degradation of the substrates. Micro-autophagy involves invagination or protrusion of the vacuole, which is formed by a lysosomal membrane. It also degrades extracellular molecules encapsulated by endocytosis (receptor-mediated pathway) or pinocytosis, following fusion with lysosome. The pinocytotic vesicles fuse with endosomes to hydrolyse the substrates. Chaperone-mediated autophagy is usually a selective degradation pathway, in which the protein substrates made up of KFERQ-like motifs are recognised by chaperone HSC70 and cochaperones, such as carboxyl terminus of HSC70-interacting protein (CHIP), heat shock protein 40 (HSP40) and HSP70-HSP90 organizing protein (HOP), and are transferred into the lysosome via a lysosomal receptor complex, LAMP-2. (1) Macro-autophagy has been considered as a nonselective cellular process; however, Fasudil HCl tyrosianse inhibitor this autophagy controls the quality of cellular contents via selective execution (e.g., long-lived proteins, aggregated proteins, damaged organelles, and intracellular pathogens) [29]. The.