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Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan
Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651825/ https://www.ncbi.nlm.nih.gov/pubmed/37086368 http://dx.doi.org/10.1007/s11357-023-00796-4 |
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author | Phua, Cheryl Zi Jin Zhao, Xiaqing Turcios-Hernandez, Lesly McKernan, Morrigan Abyadeh, Morteza Ma, Siming Promislow, Daniel Kaeberlein, Matt Kaya, Alaattin |
author_facet | Phua, Cheryl Zi Jin Zhao, Xiaqing Turcios-Hernandez, Lesly McKernan, Morrigan Abyadeh, Morteza Ma, Siming Promislow, Daniel Kaeberlein, Matt Kaya, Alaattin |
author_sort | Phua, Cheryl Zi Jin |
collection | PubMed |
description | Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain’s proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-023-00796-4. |
format | Online Article Text |
id | pubmed-10651825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-106518252023-04-22 Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan Phua, Cheryl Zi Jin Zhao, Xiaqing Turcios-Hernandez, Lesly McKernan, Morrigan Abyadeh, Morteza Ma, Siming Promislow, Daniel Kaeberlein, Matt Kaya, Alaattin GeroScience Original Article Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain’s proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-023-00796-4. Springer International Publishing 2023-04-22 /pmc/articles/PMC10651825/ /pubmed/37086368 http://dx.doi.org/10.1007/s11357-023-00796-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Phua, Cheryl Zi Jin Zhao, Xiaqing Turcios-Hernandez, Lesly McKernan, Morrigan Abyadeh, Morteza Ma, Siming Promislow, Daniel Kaeberlein, Matt Kaya, Alaattin Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title | Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title_full | Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title_fullStr | Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title_full_unstemmed | Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title_short | Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
title_sort | genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651825/ https://www.ncbi.nlm.nih.gov/pubmed/37086368 http://dx.doi.org/10.1007/s11357-023-00796-4 |
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