Group Leader/s
Head of lab
intro
Deficiencies in the mitochondrial oxidative phosphorylation (OXPHOS) system are the leading cause of inborn metabolic disorders, encompassing over 350 genetic conditions with highly diverse clinical manifestations, affecting more than 1 in 4,500 newborns globally. The proper function of the OXPHOS system relies on five large multiprotein complexes embedded in the inner mitochondrial membrane. Mutations that disrupt the assembly or stability of these complexes result in isolated or combined defects in one or more OXPHOS complexes, reducing ATP production and impairing the function of affected tissues. These complexes are organized into higher-order structures called supercomplexes and respirasomes, which are thought to prevent destabilization or degradation of individual complexes and optimize the OXPHOS system's efficiency in response to metabolic changes and varying cellular energy demands. Thus, proper assembly of OXPHOS complexes and supercomplexes is critical for maintaining mitochondrial function under diverse physiological conditions and plays a key role in the development of neurodegenerative and metabolic diseases. Our research focuses on elucidating the cellular and molecular mechanisms underlying primary OXPHOS system defects, identifying and validating novel biomarkers and therapeutic targets for mitochondrial respiratory chain disorders, and investigating the regulatory processes governing OXPHOS biogenesis in both health and disease.
Members
| Cristina Ugalde Bilbao |
| Alba Cantalejo Rodrigo |
| Paula San Roman Ruiz |
Selected Publications
Liang Chao, Padavannil Abhilash, Zhang Shan, Beh Sheryl, Robinson David R.L., Meisterknecht Jana, Cabrera-Orefice Alfredo, Koves Timothy R., Watanabe Chika, Watanabe Miyuki, Illescas María, Lim Radiance, Johnson Jordan M., Ren Shuxun, Wu Ya-Jun, Kappei Dennis, Ghelli Anna Maria, Funai Katsuhiko, Osaka Hitoshi, Muoio Deborah, Ugalde Cristina, Wittig Ilka, Stroud David A., Letts James A., Ho Lena [2025]. Formation of I2+III2 supercomplex rescues respiratory chain defects. Cell Metab . 2025 Jan 8:S1550-4131(24)00457-1. doi: 10.1016/j.cmet.2024.11.011.
Baden, Pascale, Perez, Maria Jose, Raji, Hariam, Bertoli, Federico, Kalb, Stefanie, Illescas, María, Spanos, Fokion, Giuliano, Claudio, Calogero, Alessandra Maria, Oldrati, Marvin, Hebestreit, Hannah, Cappelletti, Graziella, Brockmann, Kathrin, Gasser, Thomas, Schapira, Anthony H. V., Ugalde, Cristina, Deleidi, Michela [2023]. Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism. Nat Commun. 2023 Apr 6;14(1):1930.
Fernández-Vizarra, Erika, López-Calcerrada, Sandra, Sierra-Magro, Ana, Pérez-Pérez, Rafael, Formosa, Luke E., Hock, Daniella H., Illescas, María, Peñas, Ana, Brischigliaro, Michele, Ding, Shujing, Fearnley, Ian M., Tzoulis, Charalampos, Pitceathly, Robert D.S., Arenas, Joaquín, Martín, Miguel A., Stroud, David A., Zeviani, Massimo, Ryan, Michael T., Ugalde, Cristina [2022]. Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. 2022 Nov 1;34(11):1792-1808.e6.
Fernández-Vizarra, Erika, Ugalde, Cristina [2022]. Cooperative assembly of the mitochondrial respiratory chain. Trends Biochem Sci. 2022 Dec;47(12):999-1008.
Illescas, María , Peñas, Ana , Arenas, Joaquín , Martín, Miguel A. , Ugalde, Cristina [2021]. Regulation of Mitochondrial Function by the Actin Cytoskeleton. Front Cell Dev Biol. 2021 Dec 21;9:795838.
Protasoni, Margherita, Pérez‐Pérez, Rafael, Lobo‐Jarne, Teresa, Harbour, Michael E, Ding, Shujing, Peñas, Ana, Diaz, Francisca, Moraes, Carlos T, Fearnley, Ian M, Zeviani, Massimo, Ugalde, Cristina, Fernández‐Vizarra, Erika [2020]. Respiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV. EMBO J. 2020 Feb 3;39(3):e102817.
Lobo‐Jarne, Teresa, Pérez‐Pérez, Rafael, Fontanesi, Flavia, Timón‐Gómez, Alba, Wittig, Ilka, Peñas, Ana, Serrano‐Lorenzo, Pablo, García‐Consuegra, Inés, Arenas, Joaquín, Martín, Miguel A, Barrientos, Antoni, Ugalde, Cristina [2020]. Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes. EMBO J. 2020 Jul 15;39(14):e103912.
Lobo-Jarne, Teresa, Nývltová, Eva, Pérez-Pérez, Rafael, Timón-Gómez, Alba, Molinié, Thibaut, Choi, Austin, Mourier, Arnaud, Fontanesi, Flavia, Ugalde, Cristina, Barrientos, Antoni [2018]. Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics. Cell Rep. 2018 Nov 13;25(7):1786-1799.e4.
Lobo-Jarne, Teresa, Ugalde, Cristina [2018]. Respiratory chain supercomplexes: Structures, function and biogenesis. Semin Cell Dev Biol. 2018 Apr;76:179-190.
Pérez-Pérez, Rafael, Lobo-Jarne, Teresa, Milenkovic, Dusanka, Mourier, Arnaud, Bratic, Ana, García-Bartolomé, Alberto, Fernández-Vizarra, Erika, Cadenas, Susana, Delmiro, Aitor, García-Consuegra, Inés, Arenas, Joaquín, Martín, Miguel A., Larsson, Nils-Göran, Ugalde, Cristina [2016]. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation. Cell Rep. 2016 Aug 30;16(9):2387-98.
Barrientos, Antoni, Ugalde, Cristina [2013]. I function, therefore I am: overcoming skepticism about mitochondrial supercomplexes. Cell Metab. 2013 Aug 6;18(2):147-9.
Moreno-Lastres, David, Fontanesi, Flavia, García-Consuegra, Inés, Martín, Miguel A., Arenas, Joaquín, Barrientos, Antoni, Ugalde, Cristina [2012]. Mitochondrial complex I plays an essential role in human respirasome assembly. Cell Metab. 2012 Mar 7;15(3):324-35.
Funding
NATIONAL GRANTS:
CaixaResearch Health 2024, grant HR24-00604. Mito4Neuro: Integrative characterization of the mitochondrial DNA replisome in health and disease. La Caixa Foundation. Co-PIs: Rafael Fernández-Leiro (CNIO), Borja Ibarra (IMDEA Nanociencia), Cristina Ugalde (CIB-CSIC). 01/10/2024-30/09/2027. 900.300 €.
PID2023-147288NB-I00 - Biogenetic regulation of human mitochondrial respiratory chain complex I in health and disease. Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación. PI: C. Ugalde (Centro de Investigaciones Biológicas Margarita Salas, CIB-CSIC). 01/01/2025-31/12/2027. 406.250 €.
PI20/00057 - New tools for the diagnosis and treatment of mitochondrial OXPHOS disorders. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2021-31/12/2023. 147.620 €.
S2018/BAA- 4403 - SINOXPHOS: Soluciones interdisciplinares con control de edición génica al déficit bioenergético OXPHOS. Consejería de Educación de la Comunidad Autónoma de Madrid. PI coordinador: I. López-Montero (UCM). Co-PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2019-31/12/2022. 719.900 €.
PI17/00048 - Desarrollo de una plataforma de diagnóstico no invasivo para las enfermedades OXPHOS basada en la detección de nuevos biomarcadores proteicos implicados en la disfunción mitocondrial. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2018-31/12/2020. 212.650 €.
BA17/00006 - Identificación de nuevos genes asociados a patologías mitocondriales OXPHOS mediante el desarrollo combinado de tecnologías CRISPR/Cas9 y espectrometría de masas cuantitativa. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2018-31/12/2018. 41.970 €.
PI14/00209 - Búsqueda y caracterización de biomarcadores de enfermedades mitocondriales asociadas a déficits enzimáticos del sistema OXPHOS. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2015-31/12/2017. 224.150 €.
S2010/BMD-2361 - Una nueva DNA primasa/polimerasa con un posible papel en envejecimiento. Consejería de Educación de la Comunidad Autónoma de Madrid. PI coordinador: Luis Blanco Dávila (CBMSO). Co-PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2012-31/12/2015. 644.000 €.
PI11/00182 - Identificación y validación de biomarcadores de enfermedades mitocondriales. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2012-31/12/2014. 254.319 €.
PI08/0021 - Bases moleculares y fisiopatológicas de las enfermedades multisistémicas causadas por mutaciones en genes nucleares del complejo III de la cadena respiratoria mitocondrial. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2009-31/12/2011. 266.805 €.
PI05/0379 - Bases moleculares del déficit enzimático del complejo ubiquinol:citocromo c oxidorreductasa mitocondrial. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2006-31/12/2008. 102.500 €.
CP04/00011 - Estado del respirasoma mitocondrial en pacientes con déficits de los complejos enzimáticos de la cadena respiratoria: 2D-BN-SDS-PAGE como técnica para el diagnóstico de citopatías mitocondriales. Instituto de Salud Carlos III. PI: C. Ugalde (IIS Hospital 12 de Octubre, i+12). 01/01/2005-31/12/2008. 42.050 €.
INTERNATIONAL GRANTS:
1R35GM118141 - Mitochondrial Biogenesis in Health and Disease. National Institutes of Health (NIH), USA. PI: A. Barrientos (Univ. Miami Miller School of Medicine, FL, USA). Co-PI: C. Ugalde. 01/06/2021-31/05/2026.
1R01GM105781 - The Biosynthetic Pathway of Mitochondrial Respirasomes. National Institutes of Health (NIH), USA. PI: A. Barrientos (Univ. Miami Miller School of Medicine, FL, USA). Co-PI: C. Ugalde. 01/05/2014-31/12/2017.