Reduced expression of mitochondrial complex I subunit Ndufs2 does not impact healthspan in mice

Aging in mammals leads to reduction in genes encoding the 45-subunit mitochondrial electron transport chain complex I. It has been hypothesized that normal aging and age-related diseases such as Parkinson's disease are in part due to modest decrease in expression of mitochondrial complex I subu...

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Detalles Bibliográficos
Autores: McElroy, Gregory S., Chakrabarty, Ram P., D'Alessandro, Karis B., Hu, Yuan-Shih, Vasan, Karthik, Tan, Jerica, Stoolman, Joshua S., Weinberg, Samuel E., Steinert, Elizabeth M., Reyfman, Paul A., Singer, Benjamin D., Ladiges, Warren C., Gao, Lin, López-Barneo, José, Ridge, Karen, Budinger, G. R. Scott, Chandel, Navdeep S.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/307001
Acceso en línea:http://hdl.handle.net/10261/307001
https://api.elsevier.com/content/abstract/scopus_id/85127303428
Access Level:acceso abierto
Descripción
Sumario:Aging in mammals leads to reduction in genes encoding the 45-subunit mitochondrial electron transport chain complex I. It has been hypothesized that normal aging and age-related diseases such as Parkinson's disease are in part due to modest decrease in expression of mitochondrial complex I subunits. By contrast, diminishing expression of mitochondrial complex I genes in lower organisms increases lifespan. Furthermore, metformin, a putative complex I inhibitor, increases healthspan in mice and humans. In the present study, we investigated whether loss of one allele of Ndufs2, the catalytic subunit of mitochondrial complex I, impacts healthspan and lifespan in mice. Our results indicate that Ndufs2 hemizygous mice (Ndufs2+/-) show no overt impairment in aging-related motor function, learning, tissue histology, organismal metabolism, or sensitivity to metformin in a C57BL6/J background. Despite a significant reduction of Ndufs2 mRNA, the mice do not demonstrate a significant decrease in complex I function. However, there are detectable transcriptomic changes in individual cell types and tissues due to loss of one allele of Ndufs2. Our data indicate that a 50% decline in mRNA of the core mitochondrial complex I subunit Ndufs2 is neither beneficial nor detrimental to healthspan.

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