Abstract
Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.
Highlights
Autophagy is a conserved catabolic process that is involved in cellular homeostasis and is required to maintain normal cellular physiology under stressful conditions [1]
Bacterial sensing inside the cell either by NLRs or sequestosome-1-like receptors (SLRs) recruits autophagy proteins including unc-51-like kinase (ULK) 1/2 with lipid kinase complexed with Beclin 1 and Atg16L1 to initiate membrane nucleation of the phagophore to engulf invading bacteria
Knockdown of nuclear receptor co-activator 4 (NCOA4), which is responsible for directing ferritin to autophagosome, increases iron-responsive element-binding protein 2 (IRP2)- prevent cell death by exogenous reactive oxygen species Iron storage protein called ferritin is degraded in the lysosome; resulting in a form of selective macroautophagy Reduction in tumor necrosis factor (TNF)-α induced apoptosis in gut epithelium Goblet cell function, cytokine production or NOD2, ATG16L1, and immunity-related GTPase M (IRGM) gene regulation affect pathogenesis of inflammatory bowel disease Causes biochemical disturbance, endoplasmic reticulum (ER) stress, mitochondrial dysfunction induces obesity-cardiac disorders Affects beta-cells of pancreas, insulin target tissues, glucose metabolism Perturbations in autophagic machinery in cardiomyocytes and other cardiovascular cell types Autophagy through PARP1 modulation of FoxO3a transcription in cardiomyocytes
Summary
Autophagy is a conserved catabolic process that is involved in cellular homeostasis and is required to maintain normal cellular physiology under stressful conditions [1]. The disruption of mitochondrial membrane potentials by the non-structural protein of Crimean-Congo hemorrhagic fever (CCHF) virus results in apoptosis, whereas paramyxovirus V proteins inhibit constitutively active MDA5 proteins to induce autophagy All of these viral events are related to autophagy and can provide directions for future therapies for Chikungunya (CHIKV), DENV, and Zika virus (ZIKV) infections. The processes of autophagy and apoptosis are interwoven and have been implicated in both microbial infections [54,75] and cancers [26,76] Autophagy might play both physiological and pathological roles since it is involved in overcoming cell stresses [19,77,78]. This review details the important functions of autophagy in health and disease and its key roles in disease prevention and treatment
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