Mitochondrial alterations during oxidative stress in chronic obstructive pulmonary disease

Abstract

The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention. Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance. Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways. Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins. In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy. During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction. Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase.

Keywords:

• chronic obstructive pulmonary disease
• reactive oxidative stress
• reactive nitrogen stress
• mitochondrial fission/fusion
• mitophagy

Acknowledgments

The authors gratefully acknowledge the financial support for this study provided by the Shanghai Committee of Science and Technology (16401901400), the Health Bureau of Shanghai, China (2011ZJ021) and the State Key Laboratory of Clinical Pharmacology Department of Shanghai General Hospital.

Disclosure

The authors report no conflicts of interest in this work.