Exposure of the airways to cigarette smoke (CS) is the primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS consists of a complex mixture of over 6000 chemicals including the highly reactive α,β-unsaturated aldehyde acrolein. Acrolein is thought to be responsible for a large proportion of the non-cancer disease risk associated with smoking. Emerging evidence suggest a key role for CS-induced abnormalities in mitochondrial morphology and function in airway epithelial cells in COPD pathogenesis. Although in vitro studies suggest acrolein-induced mitochondrial dysfunction in airway epithelial cells, it is unknown if in vivo inhalation of acrolein affects mitochondrial content or the pathways controlling this. In this study, rats were acutely exposed to acrolein by inhalation (nose-only; 0-4 ppm), 4 hours/day for 1 or 2 consecutive days (n=6/group). Subsequently, the activity and abundance of key constituents of mitochondrial metabolic pathways as well as expression of critical proteins and genes controlling mitochondrial biogenesis and mitophagy were investigated in lung homogenates. A transient decreasing response in protein and transcript abundance of subunits of the electron transport chain complexes was observed following acrolein inhalation. Moreover, acrolein inhalation caused a decreased abundance of key regulators associated with mitochondrial biogenesis, respectively a differential response on day 1 versus day 2. Abundance of components of the mitophagy machinery was in general unaltered in response to acrolein exposure in rat lung. Collectively, this study demonstrates that acrolein inhalation acutely and dose-dependently disrupts the molecular regulation of mitochondrial metabolism in rat lung. Hence, understanding the effect of acrolein on mitochondrial function will provide a scientifically supported reasoning to shortlist aldehydes regulation in tobacco smoke. This dataset is not publicly accessible because: EPA does not own the data and therefore EPA does not have right to publish the data. It can be accessed through the following means: Data can be obtained from corresponding author of the paper. Format: The data in this paper are collected from lung tissue that were isolated from air or acrolein-exposed Wistar Kyoto rats. All data are derived from lung tissue assessment of many biological markers associated with mitochondrial homeostasis. For these data n=8 animals were used for each group of samples.

This dataset is associated with the following publication: Tulen, C., S. Snow , P. Leermakers, U. Kodavanti, F. van Schooten, A. Opperhuizen, and A. Remels. Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 469(153129): 1, (2022).