Protein quality control in lung disease: it's all about cloud networking.

Dysfunctional protein quality control is emerging as a key pathogenic mechanism for chronic lung diseases. Two major hereditary conformational disorders of the lung, cystic fibrosis and a1-antitrypsin (a1-AT) deficiency, and some familial forms of idiopathic pulmonary fibrosis (IPF) are caused by the expression of mutant and misfolded proteins that disrupt protein homeostasis and drive the onset of pulmonary diseases [2, 3]. Disturbed proteostasis also causes sporadic respiratory diseases [1, 4]. Cigarette smoke-induced protein misfolding, aberrant proteasomal protein degradation and induction of autophagy have been observed in chronic obstructive pulmonary disease (COPD) patients and smoke-exposed mice [4, 5]. Dysregulation of autophagy and endoplasmic reticulum (ER) stress have also been implicated in cystic fibrosis, pulmonary arterial hypertension, IPF and other lung diseases [6, 7]. Impairment of protein quality control pathways exacerbates the detrimental effects of environmentally induced protein damage in lung pathogenesis [1].