Inhalation of acrolein affects the regulation of mitochondrial metabolism in the airways
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Exposure of the airways to cigarette smoke is a known risk factor for developing several lung diseases including Chronic Obstructive Pulmonary Disease (COPD). Although cigarette smoke is a complex mixture of over 6000 chemicals, acrolein, a αβ1-unsaturated aldehyde generated during the pyrolysis and combustion of tobacco, is thought to be responsible for a large proportion of the non-cancer disease risk associated with smoking. Recently, cigarette smoke-induced mitochondrial dysfunction in airway epithelial cells has been implicated in the pathogenesis of COPD. While in vitro studies suggest that acrolein can impair mitochondrial function, whether or not inhalation of acrolein in vivo affects mitochondrial content or the pathways controlling this (mitochondrial biogenesis vs mitophagy) in cells of the airways is unknown. Therefore, in the present study, rats were exposed to acrolein inhalation (nose-only; 0-4 ppm), 4h/day for 1 or 2 consecutive days (n=6/group) and the activity and abundance of key constituents of mitochondrial metabolic pathways as well as expression of key proteins controlling mitochondrial biogenesis and mitophagy were investigated. Acrolein, dose- and time-dependently, affected the activity of enzymes involved in metabolic pathways, increased mtDNA copy number and decreased protein and transcript abundance of several subunits of complexes involved in the electron transport chain. Furthermore, protein and mRNA levels of key regulators of mitochondrial biogenesis were decreased in rat lung following exposure to the highest dose of acrolein. Protein and mRNA expression of key components of the mitophagy machinery were unaltered in response to acute acrolein exposure. Collectively, these results demonstrate that acute acrolein exposure disrupts the molecular regulation of mitochondrial metabolism in rat lung.