María J Sánchez-Quintero,1– 3,* Andrea Iboleón,4,* Laura Martín Chaves,1– 3 Bárbara Pozo Vilumbrales,1,5 Ada DM Carmona-Segovia,1– 3 Pilar Martínez López,1,6 Miguel Romero-Cuevas,1– 3 Jorge Rodríguez-Capitán,1– 3 Víctor M Becerra-Muñoz,1– 3 Francisco Javier Pavón-Morón,1– 3 Mora Murri1,2,7,8 1Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Málaga, Spain; 2Unidad de Gestión Clínica Cardiología y Cirugía Cardiovascular, Hospital Universitario Virgen de la Victoria, Málaga, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; 4Unidad Docente Multiprofesional de Atención Familiar y Comunitaria. Distrito de Atención Primaria Málaga-Guadalhorce, Málaga, Spain; 5Department of Animal Biology, University of Málaga, Málaga, Spain; 6Unidad de Gestión Clínica de Cuidados Críticos y Urgencias, Medicina Intensiva. Hospital Universitario Virgen de la Victoria, Málaga, Spain; 7Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain; 8Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain*These authors contributed equally to this workCorrespondence: Francisco Javier Pavón-Morón, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Málaga, 29590, Spain, Email javier.pavon@ibima.eu Mora Murri, Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, 29010, Spain, Email moramurri@gmail.comPurpose: Aortic valve disease (AVD) is a common condition that leads to pressure and/or volume overload in the left ventricle. Aortic valve replacement is the standard treatment, as no pharmacological therapies are currently available. The incidence of AVD is increasing in developed countries, making the discovery of new biomarkers for early detection crucial. The importance of mitochondria in heart function is well established, and various cardiovascular pathologies are associated with mitochondrial dysfunction. In this cross-sectional study, we evaluated for the first time the role of mitochondria in AVD, aiming to identify new pathways involved in the disease and discover potential biomarkers.Patients and Methods: We recruited 17 patients diagnosed with AVD and scheduled for aortic valve replacement, and 22 healthy controls. Plasma levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial open reading frame of the 12S rRNA type-c peptide (MOTS-c) were measured by ELISA.Results: We observed significantly reduced levels of both proteins in patients, suggesting that substantial mitochondrial dysfunction occurs in AVD patients, independent of sex or age, but directly related to the disease.Conclusion: Mitochondria may represent a promising target for studying new pathways involved in AVD. We propose PGC1α and MOTS-c as potential plasma biomarkers for AVD detection. Further studies, including early-stage patients, are necessary to confirm the significance of our findings. Keywords: aortic valve disease, biomarkers, mitochondria, PGC-1α, MOTS-c