Abstract
Tobacco smoke-related diseases such as chronic obstructive pulmonary disease (COPD) are associated with high healthcare burden and mortality rates. Many COPD patients were reported to have muscle atrophy and weakness, with several studies suggesting intrinsic muscle mitochondrial impairment as a possible driver of this phenotype. Whereas much information has been learned about muscle pathology once a patient has COPD, little is known about how active tobacco smoking might impact skeletal muscle physiology or mitochondrial health. In this study, we examined the acute effects of cigarette smoke condensate (CSC) on muscle mitochondrial function and hypothesized that toxic chemicals present in CSC would impair mitochondrial respiratory function. Consistent with this hypothesis, we found that acute exposure of muscle mitochondria to CSC caused a dose-dependent decrease in skeletal muscle mitochondrial respiratory capacity. Next, we applied an analytical nuclear magnetic resonance (NMR)-based approach to identify 49 water-soluble and 12 lipid-soluble chemicals with high abundance in CSC. By using a chemical screening approach in the Seahorse XF96 analyzer, several CSC-chemicals, including nicotine, o-Cresol, phenylacetate, and decanoic acid, were found to impair ADP-stimulated respiration in murine muscle mitochondrial isolates significantly. Further to this, several chemicals, including nicotine, o-Cresol, quinoline, propylene glycol, myo-inositol, nitrosodimethylamine, niacinamide, decanoic acid, acrylonitrile, 2-naphthylamine, and arsenic acid, were found to significantly decrease the acceptor control ratio, an index of mitochondrial coupling efficiency.
Highlights
25% of individuals with the tobacco smoke-related disease chronic obstructive pulmonary disease (COPD) have muscle atrophy and weakness, and this contributes to low mobility-related function, increased healthcare burden, and greater mortality [1–3]
Smoking is a major risk factor for many chronic diseases, and some of the chemicals derived from tobacco smoke are known to be toxic [65]
This study found that skeletal muscle mitochondrial respiration was dose-dependently impaired by acute exposure to cigarette smoke extract
Summary
25% of individuals with the tobacco smoke-related disease chronic obstructive pulmonary disease (COPD) have muscle atrophy and weakness, and this contributes to low mobility-related function, increased healthcare burden, and greater mortality [1–3]. Mitochondrial impairments are well documented in skeletal muscle from COPD patients, including decreased oxidative capacity and elevated mitochondrial reactive oxygen species (ROS) [7,9,10]. Mitochondria are often described as the powerhouse of the cells, generating the energy required for many cell functions in the form of ATP by means of oxidative phosphorylation [11]. Both active and passive tobacco/cigarette smoke exposure decreases mitochondrial respiration and, in some cases, increases ROS across a range of cell/tissue types (nicely reviewed by Fetterman et al [12]). The degree to which acute tobacco smoke exposure can suppress mitochondrial respiratory function is unclear
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