Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

Figure 3

HO-1 as a regulator of autophagy. Autophagic machinery is mobilized in response to stress signals that result in mitochondrial perturbation or accumulations of protein aggregates. A number of proteins have been identified as signaling molecules in preautophagosomal assembly. These include master regulators such as the ULK1 complex, the Beclin-1/Vps34 complex, as well as the autophagic proteins LC3B (Atg8), Atgs 5, 12, 16 which transiently associate with the nascent autophagosome. In inflammation models, HO-1 has been implicated as an inducer of autophagy leading to cell survival and anti-inflammatory effects. In this regard, HO-1 may preserve mitochondrial integrity through the activation of mitochondrial-selective autophagy (mitophagy) which enhances cell survival. In models of neurodegeneration, overexpression of HO-1 leading to activation of autophagy/mitophagy may be detrimental and contribute to neuronal cell death. In lung epithelial cells, HO-1 prevents the induction of autophagy in response to cigarette smoke, leading to cell survival and inhibition of cell death pathways. Overall, the role of HO-1 in controlling cell fate through autophagy is complex. In limited studies to date, the effect of HO-1 on autophagy varies in a cell-type and inducer-specific fashion.