Cigarette smoke extract increases mitochondrial membrane permeability through activation of adenine nucleotide translocator (ANT) in lung epithelial cells

• Published in: Biochemical and biophysical research communications Vol. 525; no. 3; pp. 733 - 739
• Main Authors: Wu, Kaiyue, Luan, Guangxin, Xu, Yanhong, Shen, Shuang, Qian, Shengnan, Zhu, Zhen, Zhang, Xiaoying, Yin, Shaojun, Ye, Jianping
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07-05-2020
• Subjects: ANT; ATP; COPD; Mitophagy; Uncoupling; Uncoupling; Mitophagy; ATP; ANT; COPD
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.02.160

Cigarette smoke is one of major risk factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). It is generally believed that cigarette smoke induces mitochondrial damage in the alveolar epithelial cells to contribute to COPD. However, the exact molecular mechanism remains unknown for the mitochondrial damage. In this study, cigarette smoke extract (CSE) was found to induce the mitochondrial membrane permeability (MMP), which promoted proton leakage leading to the reduction in mitochondrial potential and ATP production. ANT in the mitochondrial inner membrane was activated by CSE for the alteration of MMP. The activation was observed without an alteration in the protein level of ANT. Inhibition of the ANT activity with ADP or bongkrekic acid prevented the MMP alteration and potential drop upon CSE exposure. The ANT activation was observed with a rise in ROS production, inhibition of the mitochondrial respiration, decrease in the complex III protein and rise in mitophagy activity. The results suggest that ANT may mediate the toxic effect of cigarette smoke on mitochondria and control of ANT activity is a potential strategy in intervention of the toxicity.
•Cigarette smoke extract (CSE) induced the mitochondrial membrane permeability (MMP).•The adenine nucleotide translocator (ANT) was activated for the MMP alteration.•The ANT activation was observed without an alteration in the protein level.•Inhibition of the ANT activity by small molecule chemicals attenuated the CSE toxicity.