Vall d'Hebron Talks by VHIR 'Structural and functional heterogeneity of the human respiratory chain'

Speaker: Dr. Cristina Ugalde Bilbao, scientist at the CSIC, where she will continue to develop her interests in mitochondrial translational research.

The structural organization of the mitochondrial respiratory chain (MRC) has been intensely debated for over 60 years. The mammalian MRC is formed by complexes I, III and IV that can associate in supercomplexes (SCs) and respirasomes,whose biogenetic regulation and functional properties remain unclear. We have shown the coexistence of two separated MRC organizations in human cells and postmitotic tissues, C-MRC and S-MRC, defined by the preferential expression of each of the three complex IV COX7A subunit isoforms: COX7A1, COX7A2 and COX7A2L (SCAFI). Notably, prevalence of each MRC organization is reversibly regulated by the activation state of the pyruvate dehydrogenase complex (PDC). Activated PDC promotes oxidative phosphorylation (OXPHOS) where the C-MRC organization is prevalent, whereas inactivated PDC stimulates the S-MRC organization upon metabolic rewiring of OXPHOS towards glycolysis. We show a link between the metabolic signatures converging at PDC and the structural and functional organization of the MRC, concluding that its structural heterogeneity warrants optimal adaptation to metabolic function.

CV:
Her research work focuses on the study of mitochondrial pathologies, specifically on the molecular mechanisms that regulate the biogenesis and function of the mitochondrial OXPHOS system in human cells and tissues in health and disease conditions. She has extensive experience in the translational application of genetic-molecular and biochemical-proteomic techniques, as well as in the concepts of medicine, metabolism and mitochondrial bioenergetics, with a clearly translational orientation into the diagnosis and treatment of mitochondrial pathologies.

Cristina spent a 4-year postdoctoral period at the Laboratory of Mitochondrial Disorders at the Radboud University Medical Center (Nijmegen, The Netherlands), supervised by Profs. Leo Nijtmans and Jan Smeitink. In 2005, she became a Principal Investigator (PI) of the Miguel Servet Program and joined the Laboratory of Rare, Mitochondrial and Neuromuscular Diseases (LERMN) at Hospital 12 de Octubre Research Institute (i+12, Madrid). She belongs to the CIBER for Rare Diseases (CIBERER) since 2006 and in 2011, she became an I3 Researcher of the National Health System. In 2018, she spent a sabbatical year as Guest Researcher at Prof. Mike Ryan´s lab (Monash University, Australia) in order to acquire new skills on CRISPR/Cas9 genome editing and functional proteomics. In 2023, she got a tenured scientist position at CSIC, where she will continue developing her scientific interests on mitochondrial translational research.

So far, she has published a total of 56 articles (24 as senior author, including contributions in relevant scientific journals like Cell Metabolism, Trends in Biochemical Sciences, EMBO Journal or Cell Reports). She belongs to the Editorial Board of Frontiers in Physiology and Frontiers in Cell and Developmental Biology. Finally, she was a Founder Member of the European Society for Mitochondrial Research and Medicine (E-mit Society, www.emit.org), where she is currently part of the official Executive Board.

Host: Dr. Yolanda Cámara Navarro, Main researcher, Neuromuscular and Mitochondrial Pathology (VHIR)

Registre Online: https://gencat.zoom.us/j/91648965643​