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

Abstract

Protein quality control involves the comprehensive management of protein function in the cell and is called “proteostasis” [1]. It ranges from translation and chaperone-assisted three-dimensional folding, interaction with protein partners, signal-induced post-translational modifications to disposal by the proteasome or autophagy pathways. 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 α1-antitrypsin (α1-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]. The European Respiratory Society (ERS) research seminar Protein Quality Control in Lung Disease, held on March 1–2, 2014, at Lake Starnberg in Germany, brought together international experts to develop a comprehensive view of protein quality control in general and in the lung in particular. Understanding the complex interplay of protein misfolding, ER homeostasis and protein degradation as interrelated components of adaptive proteostasis will identify novel therapeutic targets for treatment of pulmonary diseases, as outlined here.</p