Low abundance of NDUFV2 and NDUFS4 subunits of the hydrophilic complex I domain and VDAC1 predicts mammalian longevity
Natalia Mota-Martorell,
Mariona Jove,
Irene Pradas,
Isabel Sanchez,
José Gómez,
Alba Naudi,
Gustavo Barja,
Reinald Pamplona
Affiliations
Natalia Mota-Martorell
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Catalonia, Spain
Mariona Jove
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Catalonia, Spain
Irene Pradas
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Catalonia, Spain
Isabel Sanchez
Proteomics and Genomics Unit, University of Lleida, Lleida, Catalonia, Spain
José Gómez
Department of Biology and Geology, Physics and Inorganic Chemistry, University Rey Juan Carlos I, ESCET-Campus de Móstoles, Móstoles, Madrid, Spain
Alba Naudi
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Catalonia, Spain
Gustavo Barja
Department of Genetics, Physiology and Microbiology, Complutense University of Madrid, Madrid, Spain
Reinald Pamplona
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Catalonia, Spain; Corresponding author. Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Biomedicine 1 building, Av. Rovira Roure 80, Lleida, 25198, Spain.
Mitochondrial reactive oxygen species (ROS) production, specifically at complex I (Cx I), has been widely suggested to be one of the determinants of species longevity. The present study follows a comparative approach to analyse complex I in heart tissue from 8 mammalian species with a longevity ranging from 3.5 to 46 years. Gene expression and protein content of selected Cx I subunits were analysed using droplet digital PCR (ddPCR) and western blot, respectively. Our results demonstrate: 1) the existence of species-specific differences in gene expression and protein content of Cx I in relation to longevity; 2) the achievement of a longevity phenotype is associated with low protein abundance of subunits NDUFV2 and NDUFS4 from the matrix hydrophilic domain of Cx I; and 3) long-lived mammals show also lower levels of VDAC (voltage-dependent anion channel) amount. These differences could be associated with the lower mitochondrial ROS production and slower aging rate of long-lived animals and, unexpectedly, with a low content of the mitochondrial permeability transition pore in these species.
