The Underlying Role of Mitophagy in Different Regulatory Mechanisms of Chronic Obstructive Pulmonary Disease

Abstract

COPD is a common disease of the respiratory system. Inflammation, cellular senescence and necroptosis are all pathological alterations of this disease, which may lead to emphysema and infection that aggravate disease progression. Mitochondria acting as respiration-related organelles is usually observed with abnormal changes in morphology and function in CS-stimulated models and COPD patients. Damaged mitochondria can activate mitophagy, a vital mechanism for mitochondrial quality control, whereas under the persistent stimulus of CS or other forms of oxidative stress, mitophagy is impaired, resulting in insufficient clearance of damaged mitochondria. However, the excessive activation of mitophagy also seems to disturb the pathology of COPD. In this review, we demonstrate the variations in mitochondria and mitophagy in CS-induced models and COPD patients and discuss the underlying regulatory mechanism of mitophagy and COPD, including the roles of inflammation, senescence, emphysema and infection.

Keywords:

• mitophagy
• COPD
• different regulatory mechanisms

Abbreviations

AC, acetyl; CCCP, carbonyl cyanide m-chlorophenylhydrazone; CCL2, C-C motif chemokine ligand 2; COPD, Chronic obstructive pulmonary disease; CS, cigarette smoke; CSE, cigarette smoke extract; CXCL1, C-X-C motif chemokine ligand 1; DAMP, damage-associated molecular patterns; Drp1, dynamic-related protein 1; Fis1, fission-related protein 1; FOXO3, forkhead box O3; HBEC, human bronchial epithelial cell; IFN, interferon; IL, interleukin; IRF3, IFN regulatory factor 3; ISG, IFN-stimulated gene; KC, calcitonin related polypeptide alpha; KO, knockout; LRRC25, leucine-rich repeat containing protein 25; MAPK, mitogen activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MCC, mucociliary clearance; MFN, mitofusin; MKK3, mitogen activated protein kinase kinase 3; MLKL, mixed lineage kinase domain like pseudokinase; mtDNA, mitochondrial DNA; mtROS, mitochondrial ROS; NDP52, calcium binding and coiled-coil domain 2; NFκB, nuclear factor kappa B; NGLY1, N-glycanase 1; NLRP3, NLR family pyrin domain containing 3; NLRX1, NOD-like receptor X1; NRF1, nuclear factor, erythroid 2 like 1; OPA, optic atrophy; OPTN, optineurin; PD, Parkinson’s disease; PDH, pyruvate dehydrogenase; PGC-1α, peroxisome proliferator-activated receptor γ coactivator-1 α; PINK1, PTEN-induced putative kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; RIP3, receptor-interacting serine-threonine kinase 3; RIPK3, receptor-interacting protein kinase 3; RLR, RIG-I like receptor; ROS, reactive oxygen species; SIRT, sirtuin; TBK1, TANK binding kinase 1; TFAM, mitochondrial transcription factor A; TLR9, toll like receptor 9; TNFR, tumor necrosis factor receptor; TRAF, TNF receptor-associated factor; WT, wild type.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest for this work.