Cinnamon Polysaccharide Regulates FUNDC1-Dependent Mitochondrial Autophagy to Reduce Oxidative Stress-Driven Mammary Gland Aging in Dairy Cows

Abstract Mastitis causes oxidative stress, inflammation, mitochondrial dysfunction, and impaired lactation in dairy cows. This study investigated whether FUNDC1 (FUN14 domain-containing protein 1)-associated mitochondrial quality control protects mammary tissue from oxidative stress-driven senescence and whether cinnamon polysaccharide (CP) can restore this pathway during mastitis recovery. Mastitis-associated oxidative stress reduced FUNDC1 expression, disrupted mitochondrial dynamics by suppressing fusion and promoting fission, decreased mitochondrial membrane potential, and increased senescence markers in bovine mammary epithelial cells. FUNDC1 overexpression alleviated mitochondrial dysfunction and senescence-associated changes. Mechanistically, the E3 ubiquitin ligase FANCL contributed to the proteasome-dependent reduction of FUNDC1 under oxidative stress. CP treatment restored FUNDC1 expression, reduced inflammation and oxidative stress, improved mitochondrial homeostasis, and enhanced postmastitis milk-yield recovery when combined with antibiotic treatment. These findings identify the FANCL–FUNDC1 axis as a link between oxidative stress and mammary gland senescence and support CP as a functional adjunct for mastitis management.