Autophagy/Mitophagy in Airway Diseases: Impact of Oxidative Stress on Epithelial Cells

Abstract

Autophagy is the key process by which the cell degrades parts of itself within the lysosomes. It maintains cell survival and homeostasis by removing molecules (particularly proteins), subcellular organelles, damaged cytoplasmic macromolecules, and by recycling the degradation products. The selective removal or degradation of mitochondria is a particular type of autophagy called mitophagy. Various forms of cellular stress (oxidative stress (OS), hypoxia, pathogen infections) affect autophagy by inducing free radicals and reactive oxygen species (ROS) formation to promote the antioxidant response. Dysfunctional mechanisms of autophagy have been found in different respiratory diseases such as chronic obstructive lung disease (COPD) and asthma, involving epithelial cells. Several existing clinically approved drugs may modulate autophagy to varying extents. However, these drugs are nonspecific and not currently utilized to manipulate autophagy in airway diseases. In this review, we provide an overview of different autophagic pathways with particular attention on the dysfunctional mechanisms of autophagy in the epithelial cells during asthma and COPD. Our aim is to further deepen and disclose the research in this direction to stimulate the develop of new and selective drugs to regulate autophagy for asthma and COPD treatment.

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease

“…Hence, a rational position is that the assessment of lung tissues should offer more informative predictive insights, particularly for early disease. Indeed, outcomes derived from lung samples have been convincingly shown to exhibit autophagy incompetency in COPD [2,27,28]. Further, the abundance of autophagy receptors (to support LC3B-II observations) in e.g.…”

Mitochondrial Dysfunction and Nanocarrier-Based Treatments in Chronic Obstructive Pulmonary Disease (COPD)

“…[ [26][27][28][29] Mitophagy Mitophagy removes damaged mitochondria from the cell and suppresses oxidative stress. The accumulation of dysfunctional mitochondria due to impaired mitophagy in COPD leads to excessive ROS generation, resulting in further oxidative stress and cellular damage.…”

“…The accumulation of dysfunctional mitochondria due to impaired mitophagy in COPD leads to excessive ROS generation, resulting in further oxidative stress and cellular damage. [28,29] skeletal muscle dysfunction, and autophagy/mitophagy dysfunction might be related to both mitochondrial dysfunction and COPD (Table 1). These connections are being explored, but the relationship is complex and not fully understood [15].…”

“…Autophagy activation protects the lung by decreasing cellular senescence [27]. However, autophagy exerts both protective and destructive effects in COPD [28,29]. Activated autophagy increases inflammatory cytokines such as TNF-α, IL-6, and IL-8, leading to aggravating pathological processes of COPD and affecting prognosis [33].…”