Autophagy: A Crucial Moderator of Redox Balance, Inflammation, and Apoptosis in Lung Disease

Abstract

Significance: Autophagy is a fundamental cellular process that functions in the turnover of subcellular organelles and protein. Activation of autophagy may represent a cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Autophagy can increase survival during nutrient deficiency and play a multifunctional role in host defense, by promoting pathogen clearance and modulating innate and adaptive immune responses. Recent Advances: Autophagy has been described as an inducible response to oxidative stress. Once believed to represent a random process, recent studies have defined selective mechanisms for cargo assimilation into autophagosomes. Such mechanisms may provide for protein aggregate detoxification and mitochondrial homeostasis during oxidative stress. Although long studied as a cellular phenomenon, recent advances implicate autophagy as a component of human diseases. Altered autophagy phenotypes have been observed in various human diseases, including lung diseases such as chronic obstructive lung disease, cystic fibrosis, pulmonary hypertension, and idiopathic pulmonary fibrosis. Critical Issues: Although autophagy can represent a pro-survival process, in particular, during nutrient starvation, its role in disease pathogenesis may be multifunctional and complex. The relationship of autophagy to programmed cell death pathways is incompletely defined and varies with model system. Future Directions: Activation or inhibition of autophagy may be used to alter the progression of human diseases. Further resolution of the mechanisms by which autophagy impacts the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid. Redox Signal. 20,

Upregulation of autophagy decreases chlorine-induced mitochondrial injury and lung inflammation

“…These data suggests a dynamic restoration of the mitochondrial population through quality control mechanisms. Autophagy is essential for this process since it removes damaged cytosolic and mitochondrial organelles, which are sequestered and delivered to lysosomes for degradation and recycling [24, 48, 49]. Proteins or organelles modified by reactive species are targeted for removal by the lysosomal-autophagy system and the selective removal of mitochondria by mitophagy is a critical step in maintaining mitochondrial quality control [1, 24, 25, 32].…”

“…There is considerable debate as to whether autophagy contributes to or mitigates the pathology of pulmonary disease [24, 48]. For example, Chen et al .…”

Activation of autophagy in macrophages by pro-resolving lipid mediators

“…The balance between apoptosis and autophagy has been recognized to be essential in the determination of the life span of macrophages within the inflammatory context. 16 In recent years it has become evident that both processes exhibit substantial molecular crosstalk that is not yet fully understood. 17 We have demonstrated that LXA 4 increases macrophage survival via inhibition of the apoptotic process.…”

Autophagy in glaucoma: Crosstalk with apoptosis and its implications

“…[36,56,77,78] and other physiological/pathophysiological processes, such as development, differentiation [42], anti-aging, elimination of microorganisms, cell death, tumor suppression and antigen presentation in the body [14,48]. In responses to stress, the primary function of autophagy is thought to aid cellular survival by recycling damaged organelles and misfolded proteins to provide energy and substrates for reconstruction [44].…”