KAUST Research Workshop on Innovative Technologies to Study Brain Energy Metabolism
Spanish National Centre for Cardiovascular Research, Madrid
Professor José Antonio Enríquez ia a scientist with a wide experience in biogenesis and pathology of mtDNA. He currently works at the Department of Cardiovascular Development and Repair (DRC), Spanish National Centre for Cardiovascular Research. José does research in Cancer Research, Cell Biology and Molecular Biology. Their current project is 'Research on mitochondria.'
José Antonio Enríquez1 Centro Nacional de Investigaciones Cardiovasculares Carlos III; Madrid (SPAIN)2 CIBERFES C/ Melchor Fernández-Almagro 3, 28029 Madrid, (SPAIN)Animal models with identical nuclear genomes but with different mtDNA haplotypes (conplastic mice) generate functionally different OXPHOS systems that shape the organismal metabolism and determine heathy ageing1, supporting the conclusion that different mtDNA wild type haplotypes are phenotypically relevant. We will discuss the molecular basis of this influence and at what extension is the interaction mtDNA/nDNA or just the mtDNA variant what matters.Mitochondrial DNA (mtDNA) is present in multiple copies in each nucleated cell of our body, all derived from the clonal expansions of those in the oocyte. Therefore, all mtDNAs of a given cell are essentially identical, a situation named homoplasmy. Heteroplasmy refers to the presence of more than one variant of mtDNA co-existing in the same cytoplasm. Heteroplasmy is actively combated by several mechanisms, including degradation of the paternal mtDNA upon fertilization, and the existence of a genetic mtDNA bottleneck in oocyte development. Heteroplasmy may be naturally generated by mutagenesis during mtDNA replication, but also can be caused by novel medical technologies. We will explore the unsolved controversy regarding the possible functional consequences of the impact of heteroplasmy in OXPHOS performance. 1Latorre-Pellicer, A. et al. Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing. Nature 535, 561–565 (2016).