The Role of Autophagy in Lung Disease

The autophagy degradation pathway is a cellular pathway that sequesters cargo from the cytosol to autophagosomes that are transferred to lysosomes for degradation or recycled as precursor metabolites. The autophagy pathway allows the removal of damaged organelles/proteins and is emerging as an important aspect of multiple human pulmonary diseases. The autophagy process is important in both the function of the immune system and the control of inflammation. Xenophagy (autophagy of bacteria) is an example of selective autophagy which could play a role in host defense mechanisms in pulmonary diseases such as sepsis. Autophagy pathways involving the degradation of cytosolic cargo could play different roles in disease pathogenesis and progression. In the case of certain lung diseases, mitophagy is elevated and the cilia shorten (ciliophagy), which contribute to lung dysfunction in the pathogenesis of chronic obstructive pulmonary disease. In other types of lung diseases such as pulmonary vascular disease, autophagy may provide a protective role to allow cell proliferation, repair and control of cell death. Disruption of autophagy in cystic fibrosis and idiopathic pulmonary fibrosis could promote pathogenesis of the disease. In lung cancer, autophagy is a ‘double-edged sword’ it blocks progression, but at the same time promotes tumor growth. In this chapter, we will review the different types of autophagy, the role of autophagy and its significance to human lung diseases. In addition, we will discuss the potential of targeting autophagy with therapeutics for lung disease management.