Longevity & AgingMitochondrial Peptide MOTS-c Shields Lungs From Reperfusion Injury via Novel Nuclear Pathway
Researchers discovered that MOTS-c, a 16-amino acid peptide encoded in mitochondrial DNA, protects lung endothelial cells during ischemia-reperfusion injury by translocating into the nucleus via a MYH9-dependent mechanism. During oxidative stress, reactive oxygen species activate the kinase CK2A, which phosphorylates MYH9 at Ser1943, enabling MOTS-c to bind the MYH9-γ-actin complex and travel to the nucleus. Once there, MOTS-c directly activates antioxidant genes like HMOX1 and NQO1 via antioxidant response elements. In 150 cardiac surgery patients, rising serum MOTS-c levels over 24 hours post-bypass (ΔMOTS-c) predicted ARDS with an AUC of 0.885. Exogenous MOTS-c administration in rat models reduced lung damage, inflammation, and mortality.
