Oncotarget

Research Papers:

Acrolein induces mtDNA damages, mitochondrial fission and mitophagy in human lung cells

Hsiang-Tsui Wang _, Jing-Heng Lin, Chun-Hsiang Yang, Chun-Hao Haung, Ching-Wen Weng, Anya Maan-Yuh Lin, Yu-Li Lo, Wei-Shen Chen and Moon-Shong Tang

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Oncotarget. 2017; 8:70406-70421. https://doi.org/10.18632/oncotarget.19710

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Abstract

Hsiang-Tsui Wang1, Jing-Heng Lin1, Chun-Hsiang Yang1, Chun-Hao Haung1, Ching-Wen Weng1, Anya Maan-Yuh Lin1,2,3, Yu-Li Lo1, Wei-Shen Chen4 and Moon-Shong Tang4

1Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan

2Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan

3Department of Medical Research, Taipei Veterans, General Hospital, Taipei, Taiwan

4Department of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, New York, NY, USA

Correspondence to:

Hsiang-Tsui Wang, email: [email protected]

Keywords: acrolein, ROS, mtDNA damages, mitochondrial fission, mitophagy

Received: May 04, 2017     Accepted: June 28, 2017     Published: July 31, 2017

ABSTRACT

Acrolein (Acr), a highly reactive unsaturated aldehyde, can cause various lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. We have found that Acr can damage not only genomic DNA but also DNA repair proteins causing repair dysfunction and enhancing cells’ mutational susceptibility. While these effects may account for Acr lung carcinogenicity, the mechanisms by which Acr induces lung diseases other than cancer are unclear. In this study, we found that Acr induces damages in mitochondrial DNA (mtDNA), inhibits mitochondrial bioenergetics, and alters mtDNA copy number in human lung epithelial cells and fibroblasts. Furthermore, Acr induces mitochondrial fission which is followed by autophagy/ mitophagy and Acr-induced DNA damages can trigger apoptosis. However, the autophagy/ mitophagy process does not change the level of Acr-induced mtDNA damages and apoptosis. We propose that Acr-induced mtDNA damages trigger loss of mtDNA via mitochondrial fission and mitophagy. These processes and mitochondria dysfunction induced by Acr are causes that lead to lung diseases.


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