Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice
Cisd2 (CDGSH iron sulfur domain 2) is a pro-longevity gene that extends the lifespan and health span of mice, ameliorates age-associated structural damage and limits functional decline in multiple tissues. Non-alcoholic fatty liver disease (NAFLD), which plays an important role in age-related liver...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/9/1229 |
| _version_ | 1797520123006812160 |
|---|---|
| author | Chen-Hua Huang Yi-Long Huang Zhao-Qing Shen Chao-Hsiung Lin Ting-Fen Tsai |
| author_facet | Chen-Hua Huang Yi-Long Huang Zhao-Qing Shen Chao-Hsiung Lin Ting-Fen Tsai |
| author_sort | Chen-Hua Huang |
| collection | DOAJ |
| description | Cisd2 (CDGSH iron sulfur domain 2) is a pro-longevity gene that extends the lifespan and health span of mice, ameliorates age-associated structural damage and limits functional decline in multiple tissues. Non-alcoholic fatty liver disease (NAFLD), which plays an important role in age-related liver disorders, is the most common liver disease worldwide. However, no medicines that can be used to specifically and effectively treat NAFLD are currently approved for this disease. Our aim was to provide pathological and molecular evidence to show that Cisd2 protects the liver from age-related dysregulation of lipid metabolism and protein homeostasis. This study makes four major discoveries. Firstly, a persistently high level of Cisd2 protects the liver from age-related fat accumulation. Secondly, proteomics analysis revealed that Cisd2 ameliorates age-related dysregulation of lipid metabolism, including lipid biosynthesis and β-oxidation, in mitochondria and peroxisomes. Thirdly, Cisd2 attenuates aging-associated oxidative modifications of proteins. Finally, Cisd2 regulates intracellular protein homeostasis by maintaining the functionality of molecular chaperones and protein synthesis machinery. Our proteomics findings highlight Cisd2 as a novel molecular target for the development of therapies targeting fatty liver diseases, and these new therapies are likely to help prevent subsequent malignant progression to cirrhosis and hepatocellular carcinoma. |
| first_indexed | 2024-03-10T07:52:22Z |
| format | Article |
| id | doaj.art-82d0f68f104146a4b0c25a890ae522ac |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:22Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-82d0f68f104146a4b0c25a890ae522ac2023-11-22T12:08:57ZengMDPI AGBiomedicines2227-90592021-09-0199122910.3390/biomedicines9091229Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of MiceChen-Hua Huang0Yi-Long Huang1Zhao-Qing Shen2Chao-Hsiung Lin3Ting-Fen Tsai4Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, TaiwanCisd2 (CDGSH iron sulfur domain 2) is a pro-longevity gene that extends the lifespan and health span of mice, ameliorates age-associated structural damage and limits functional decline in multiple tissues. Non-alcoholic fatty liver disease (NAFLD), which plays an important role in age-related liver disorders, is the most common liver disease worldwide. However, no medicines that can be used to specifically and effectively treat NAFLD are currently approved for this disease. Our aim was to provide pathological and molecular evidence to show that Cisd2 protects the liver from age-related dysregulation of lipid metabolism and protein homeostasis. This study makes four major discoveries. Firstly, a persistently high level of Cisd2 protects the liver from age-related fat accumulation. Secondly, proteomics analysis revealed that Cisd2 ameliorates age-related dysregulation of lipid metabolism, including lipid biosynthesis and β-oxidation, in mitochondria and peroxisomes. Thirdly, Cisd2 attenuates aging-associated oxidative modifications of proteins. Finally, Cisd2 regulates intracellular protein homeostasis by maintaining the functionality of molecular chaperones and protein synthesis machinery. Our proteomics findings highlight Cisd2 as a novel molecular target for the development of therapies targeting fatty liver diseases, and these new therapies are likely to help prevent subsequent malignant progression to cirrhosis and hepatocellular carcinoma.https://www.mdpi.com/2227-9059/9/9/1229Cisd2non-alcoholic fatty liver diseaseaginglipid metabolismmitochondriaprotein homeostasis |
| spellingShingle | Chen-Hua Huang Yi-Long Huang Zhao-Qing Shen Chao-Hsiung Lin Ting-Fen Tsai Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice Biomedicines Cisd2 non-alcoholic fatty liver disease aging lipid metabolism mitochondria protein homeostasis |
| title | Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice |
| title_full | Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice |
| title_fullStr | Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice |
| title_full_unstemmed | Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice |
| title_short | Cisd2 Preserves the Youthful Pattern of the Liver Proteome during Natural Aging of Mice |
| title_sort | cisd2 preserves the youthful pattern of the liver proteome during natural aging of mice |
| topic | Cisd2 non-alcoholic fatty liver disease aging lipid metabolism mitochondria protein homeostasis |
| url | https://www.mdpi.com/2227-9059/9/9/1229 |
| work_keys_str_mv | AT chenhuahuang cisd2preservestheyouthfulpatternoftheliverproteomeduringnaturalagingofmice AT yilonghuang cisd2preservestheyouthfulpatternoftheliverproteomeduringnaturalagingofmice AT zhaoqingshen cisd2preservestheyouthfulpatternoftheliverproteomeduringnaturalagingofmice AT chaohsiunglin cisd2preservestheyouthfulpatternoftheliverproteomeduringnaturalagingofmice AT tingfentsai cisd2preservestheyouthfulpatternoftheliverproteomeduringnaturalagingofmice |