Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes
Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear ge...
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| Veröffentlicht in: | Nature aging 2024-08, Vol.4 (8), p.1076-1088 |
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| creator | Tao, Mei Chen, Jiani Cui, Chunlai Xu, Yandong Xu, Jingxiu Shi, Zheyi Yun, Jiaqi Zhang, Junwei Ou, Guo-Zheng Liu, Chao Chen, Yun Zhu, Zeng-Rong Pan, Ronghui Xu, Suhong Chen, Xue-Xin Rokas, Antonis Zhao, Yang Wang, Sibao Huang, Jianhua Shen, Xing-Xing |
| description | Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals. |
| doi_str_mv | 10.1038/s43587-024-00641-z |
| format | Article |
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The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.</description><identifier>ISSN: 2662-8465</identifier><identifier>EISSN: 2662-8465</identifier><identifier>DOI: 10.1038/s43587-024-00641-z</identifier><identifier>PMID: 38834883</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Caenorhabditis elegans - genetics ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Cellular Senescence - genetics ; Evolution, Molecular ; Genome, Insect - genetics ; Humans ; Insecta - genetics ; Longevity - genetics ; Mitochondria - genetics ; Mitochondria - metabolism ; Oxidative Phosphorylation</subject><ispartof>Nature aging, 2024-08, Vol.4 (8), p.1076-1088</ispartof><rights>2024. 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The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.</description><subject>Animals</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Cellular Senescence - genetics</subject><subject>Evolution, Molecular</subject><subject>Genome, Insect - genetics</subject><subject>Humans</subject><subject>Insecta - genetics</subject><subject>Longevity - genetics</subject><subject>Mitochondria - genetics</subject><subject>Mitochondria - metabolism</subject><subject>Oxidative Phosphorylation</subject><issn>2662-8465</issn><issn>2662-8465</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMtOwzAQRS0Eoqj0B1ggL9kE_IrjLBHiUQmJDawtx5mkRklcbKdS-_WktCAWo5nFuVeag9AVJbeUcHUXBc9VkREmMkKkoNnuBF0wKVmmhMxP_90ztIjxkxDCcsqJZOdoxpXiYpoL1C5rGJJrnDXJ-QH7Bhvc-aGFjUtb3MIAOK2CH9sVho3vxj1lwhYHkwBbvzHB_SXdEMEm3Lvks2G0HZiwb_A9xEt01pguwuK45-jj6fH94SV7fXtePty_ZpYqkbKqLJtayryqmKptJTktFXBjjbCKVkUjSFHkpqBc5lbKsrRGNYYVOdRlSQ1UfI5uDr3r4L9GiEn3LlroOjOAH6OeBIiSUaLIhLIDaoOPMUCj18H102-aEr13rA-O9eRY_zjWuyl0fewfqx7qv8ivUf4NDRp57w</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Tao, Mei</creator><creator>Chen, Jiani</creator><creator>Cui, Chunlai</creator><creator>Xu, Yandong</creator><creator>Xu, Jingxiu</creator><creator>Shi, Zheyi</creator><creator>Yun, Jiaqi</creator><creator>Zhang, Junwei</creator><creator>Ou, Guo-Zheng</creator><creator>Liu, Chao</creator><creator>Chen, Yun</creator><creator>Zhu, Zeng-Rong</creator><creator>Pan, Ronghui</creator><creator>Xu, Suhong</creator><creator>Chen, Xue-Xin</creator><creator>Rokas, Antonis</creator><creator>Zhao, Yang</creator><creator>Wang, Sibao</creator><creator>Huang, Jianhua</creator><creator>Shen, Xing-Xing</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5765-1419</orcidid><orcidid>https://orcid.org/0000-0002-8703-3678</orcidid><orcidid>https://orcid.org/0000-0001-6509-1765</orcidid><orcidid>https://orcid.org/0000-0002-5880-0815</orcidid><orcidid>https://orcid.org/0000-0002-7248-6551</orcidid></search><sort><creationdate>20240801</creationdate><title>Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes</title><author>Tao, Mei ; 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| ispartof | Nature aging, 2024-08, Vol.4 (8), p.1076-1088 |
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| subjects | Animals Caenorhabditis elegans - genetics Cell Nucleus - genetics Cell Nucleus - metabolism Cellular Senescence - genetics Evolution, Molecular Genome, Insect - genetics Humans Insecta - genetics Longevity - genetics Mitochondria - genetics Mitochondria - metabolism Oxidative Phosphorylation |
| title | Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes |
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