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, Moon Shong Tang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)70406-70421
Number of pages16
JournalOncotarget
Volume8
Issue number41
DOIs
StatePublished - 2017

Keywords

  • Acrolein
  • Mitochondrial fission
  • Mitophagy
  • MtDNA damages
  • ROS

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