TY - JOUR
T1 - Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice
AU - Reid, Kim
AU - Daniels, Eileen G.
AU - Vasam, Goutham
AU - Kamble, Rashmi
AU - Janssens, Georges E.
AU - Hu, Iman M.
AU - Green, Alexander E.
AU - Houtkooper, Riekelt H.
AU - Menzies, Keir J.
N1 - Funding Information: We thank the Institut Clinique de la Souris—PHENOMIN for the establishment of the Mrpl54 mouse mutant line. From the University of Ottawa, we thank the following people: Adriana Gambarotta for her IVF expertise; Dr. Kerstin Ure, Mirela Barclay, and Sarah Kealey from the Behavioural Core Unit for help with CLAMS; the staff at the Animal Care and Veterinary Services Unit, in particular Courtney Reeks and Christine Kitchen, for help in mouse-handling training and colony maintenance assistance; and Prof. Daniel Figeys for mass spectrophotometry proteomics collaboration (NorthOmics). This project was financially supported by the following: CIHR grant (MOP 159455), NSERC Collaborative Research and Training Experience program grant (RGPIN 2018-06838), and NSERC Discovery grant (DGECR 2018-00012) to K.J.M.; VIDI grant (917.15.305) to R.H.H., NSERC CGS-D scholarship awarded to K.R., UvA Lustrum 385 grant to E.G.D., and uOttawa Brain and Mind Research Institute Eric Poulain Centre for Neuromuscular Disease Scholarship in Translational Research awarded to A.E.G. Funding Information: We thank the Institut Clinique de la Souris—PHENOMIN for the establishment of the Mrpl54 mouse mutant line. From the University of Ottawa, we thank the following people: Adriana Gambarotta for her IVF expertise; Dr. Kerstin Ure, Mirela Barclay, and Sarah Kealey from the Behavioural Core Unit for help with CLAMS; the staff at the Animal Care and Veterinary Services Unit, in particular Courtney Reeks and Christine Kitchen, for help in mouse-handling training and colony maintenance assistance; and Prof. Daniel Figeys for mass spectrophotometry proteomics collaboration (NorthOmics). This project was financially supported by the following: CIHR grant (MOP 159455), NSERC Collaborative Research and Training Experience program grant (RGPIN 2018-06838), and NSERC Discovery grant (DGECR 2018-00012) to K.J.M.; VIDI grant (917.15.305) to R.H.H., NSERC CGS-D scholarship awarded to K.R., UvA Lustrum 385 grant to E.G.D., and uOttawa Brain and Mind Research Institute Eric Poulain Centre for Neuromuscular Disease Scholarship in Translational Research awarded to A.E.G. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice. In this study, we tested whether partially reducing the gene expression of a critical MRP, Mrpl54, reduced mitochondrial DNA-encoded protein content, induced the UPRmt, and affected lifespan or metabolic health using germline heterozygous Mrpl54 mice. Despite reduced Mrpl54 expression in multiple organs and a reduction in mitochondrial-encoded protein expression in myoblasts, we identified few significant differences between male or female Mrpl54 +/− and wild type mice in initial body composition, respiratory parameters, energy intake and expenditure, or ambulatory motion. We also observed no differences in glucose or insulin tolerance, treadmill endurance, cold tolerance, heart rate, or blood pressure. There were no differences in median life expectancy or maximum lifespan. Overall, we demonstrate that genetic manipulation of Mrpl54 expression reduces mitochondrial-encoded protein content but is not sufficient to improve healthspan in otherwise healthy and unstressed mice.
AB - Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice. In this study, we tested whether partially reducing the gene expression of a critical MRP, Mrpl54, reduced mitochondrial DNA-encoded protein content, induced the UPRmt, and affected lifespan or metabolic health using germline heterozygous Mrpl54 mice. Despite reduced Mrpl54 expression in multiple organs and a reduction in mitochondrial-encoded protein expression in myoblasts, we identified few significant differences between male or female Mrpl54 +/− and wild type mice in initial body composition, respiratory parameters, energy intake and expenditure, or ambulatory motion. We also observed no differences in glucose or insulin tolerance, treadmill endurance, cold tolerance, heart rate, or blood pressure. There were no differences in median life expectancy or maximum lifespan. Overall, we demonstrate that genetic manipulation of Mrpl54 expression reduces mitochondrial-encoded protein content but is not sufficient to improve healthspan in otherwise healthy and unstressed mice.
UR - http://www.scopus.com/inward/record.url?scp=85160100549&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-023-35196-3
DO - https://doi.org/10.1038/s41598-023-35196-3
M3 - Article
C2 - 37225705
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 8391
ER -