Circulating Levels of Mitochondrial Oxidative Stress-related Peptides MOTS-c and Romo1 in Stable COPD: A Cross-sectional Study

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD).

Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD.

Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c ( = 0.02) and higher levels of Romo1 ( = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, = 0.009).

Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation.

Trial Registration: www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.