Publikationsdatum:
2016-07-28
Beschreibung:
Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing Nature 535, 7613 (2016). doi:10.1038/nature18618 Authors: Ana Latorre-Pellicer, Raquel Moreno-Loshuertos, Ana Victoria Lechuga-Vieco, Fátima Sánchez-Cabo, Carlos Torroja, Rebeca Acín-Pérez, Enrique Calvo, Esther Aix, Andrés González-Guerra, Angela Logan, María Luisa Bernad-Miana, Eduardo Romanos, Raquel Cruz, Sara Cogliati, Beatriz Sobrino, Ángel Carracedo, Acisclo Pérez-Martos, Patricio Fernández-Silva, Jesús Ruíz-Cabello, Michael P. Murphy, Ignacio Flores, Jesús Vázquez & José Antonio Enríquez Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability. Many studies suggest that mtDNA variants may be associated with ageing or diseases, although mechanistic evidence at the molecular level is lacking. Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains.
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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