People with stable COPD have less of the mitochondrial peptide MOTS‑c in their blood and more of another peptide called Romo1, which is linked to oxidative stress. Lower MOTS‑c levels were tied to drops in oxygen levels during activity and poorer performance on a 6‑minute walk test, while higher Romo1 levels were linked to current smoking and lower resting oxygen saturation.

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). 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. Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (<i>p</i> = 0.02) and higher levels of Romo1 (<i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.005) and walking &lt;350 meters (OR 3.246 95% CI 1.229-8.577, <i>p</i> = 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, <i>p</i> = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, <i>p</i> = 0.009). 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. www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.