Cancer Education

Abstract

Mitochondrial function is reduced in aged tissue and upon exposure to environmental challenges. However, little is known on the adaptive response of lung cell mitochondria to non-toxic doses of cigarette smoke mimicking a realistic exposure scenario. Depending on the stress, mitochondria either adapt using a sophisticated quality control or induce dysfunction, mitophagy and apoptotic cell death. The aim of our project is to investigate the effect of non-toxic cigarette smoke on lung cell mitochondrial function and quality control. In order to analyze mitochondrial quality control in response to smoke exposure, we used a cell culture model of cigarette smoke extract (CSE) treated alveolar epithelial cells. Levels of proteins involved in mitochondrial dynamics, mitophagy and the proteasomal pathway were assessed using Western Blot analysis. Mitochondrial morphology was analyzed and mitochondrial function was determined by measuring membrane potential and activity. First data showed that non-toxic doses of CSE induced mitochondrial elongation accompanied by increased metabolic activity and membrane potential. Correspondingly, the mitochondrial fusion protein Mfn2 was found to be increased in CSE treated cells. Of note, Mfn2 levels were also increased in lungs of COPD patients. Furthermore, VCP/p97, which is proposed to extract proteins from the mitochondria and transport them to the proteasome, was upregulated in CSE treated cells as well as in COPD lungs. These data give first evidence for adaptive alterations in mitochondrial dynamics and increased mitochondrial function and UPS-mediated quality control in alveolar epithelial cells in response to non-toxic and low dose cigarette smoke.