The crosslinks between ferroptosis and autophagy in asthma

Abstract

Autophagy is an evolutionarily conserved cellular process capable of degrading various biological molecules and organelles via the lysosomal pathway. Ferroptosis is a type of oxidative stress-dependent regulated cell death associated with the iron accumulation and lipid peroxidation. The crosslinks between ferroptosis and autophagy have been focused on since the dependence of ferroptosis on autophagy was discovered. Although the research and theories on the relationship between autophagy and ferroptosis remain scattered and fragmented, the crosslinks between these two forms of regulated cell death are closely related to the treatment of various diseases. Thereof, asthma as a chronic inflammatory disease has a tight connection with the occurrence of ferroptosis and autophagy since the crosslinked signal pathways may be the crucial regulators or exactly regulated by cells and secretion in the immune system. In addition, non-immune cells associated with asthma are also closely related to autophagy and ferroptosis. Further studies of cross-linking asthma inflammation with crosslinked signaling pathways may provide us with several key molecules that regulate asthma through specific regulators. The crosslinks between autophagy and ferroptosis provide us with a new perspective to interpret and understand the manifestations of asthma, potential drug discovery targets, and new therapeutic options to effectively intervene in the imbalance caused by abnormal inflammation in asthma. Herein, we introduce the main molecular mechanisms of ferroptosis, autophagy, and asthma, describe the role of crosslinks between ferroptosis and autophagy in asthma based on their common regulatory cells or molecules, and discuss potential drug discovery targets and therapeutic applications in the context of immunomodulatory and symptom alleviation.

The association between ferroptosis and autophagy in cardiovascular diseases

“…In recent years, potential cross-linking between ferroptosis and autophagy has been found in a variety of cells treated with various compounds. 91 Further studies have found that the cross-linking of ferroptosis and autophagy may be closely related to a variety of signaling pathways. 92 Single inhibition of ferroptosis or autophagy can reverse the negative effects of compounds on cells.…”

“…The relationship between the two needs to be clarified. In recent years, potential cross‐linking between ferroptosis and autophagy has been found in a variety of cells treated with various compounds 91 . Further studies have found that the cross‐linking of ferroptosis and autophagy may be closely related to a variety of signaling pathways 92 .…”

Rational design of a lysosome-targeted fluorescent probe for monitoring the generation of hydroxyl radicals in ferroptosis pathways

“…[17][18][19][20] Moreover, accumulating evidence suggest that lysosomes are not only participants in the autophagy process, but also vital iron storage hubs in cells. [21][22][23][24][25][26] For instance, ferritinophagy, the autophagic degradation of ferritin, triggers the release of iron in lysosomes. 27 Moreover, lysosomal dysfunction can induce lysosomal membrane permeabilization (LMP), resulting in the release of considerable iron into the cytoplasm, further enhancing cell-intrinsic Fenton chemistry.…”

Cell-type-specific role of P2Y2 receptor in HDM-driven model of allergic airway inflammation

“…Asthma is a chronic inflammatory disease (1) with an increasing prevalence affecting approximately 262 million in 2019, and it was responsible for 21.6 million disability-adjusted life years (DALYs) in the same year (2). Clinical symptoms are recurring breathlessness and wheezing accompanied by airway obstruction, bronchial hyperresponsiveness, and airway inflammation (3).…”