A novel role of the mitochondrial iron-sulfur cluster assembly protein ISCU-1/ISCU in longevity and stress response
| Autor: | Shayla Curry, Mason Oliver, Yi Sheng, Sung Min Han, Christiaan Leeuwenburgh, Rui Xiao, Kaitlyn Casey, Guang Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Iron-sulfur cluster assembly
Iron-Sulfur Proteins Aging media_common.quotation_subject Iron Phosphatase Longevity Mitochondrion Biology Cell biology Mitochondria Sulfonylurea Compounds Nuclear receptor biology.protein Animals Original Article ISCU Geriatrics and Gerontology Bacterial outer membrane Caenorhabditis elegans Transcription factor Sulfur media_common |
| Zdroj: | GeroScience |
| Popis: | As an ancient cellular co-factor ubiquitously present in all domains of life, nearly all iron-sulfur ([Fe-S]) clusters are assembled in the mitochondrion. Although multiple mitochondrion-derived signalings are known to be key players in longevity regulation, whether the mitochondrial [Fe-S] cluster assembly machinery modulates lifespan is previously unknown. Here, we find that ISCU-1, the C. elegans ortholog of the evolutionarily conserved iron-sulfur cluster (ISC) assembly machinery central protein ISCU, regulates longevity and stress response. Specifically, ISCU-1 accelerates aging in the intestine. Moreover, we identify the Nrf2 transcription factor SKN-1 and a nuclear hormone receptor NHR-49 as the downstream factors of ISCU-1. Lastly, a mitochondrial outer membrane protein phosphatase PGAM-5 appears to link ISCU-1 to SKN-1 and NHR-49 in lifespan regulation. Together, we have identified a novel function of mitochondrial ISC assembly machinery in longevity modulation and stress response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00327-z. |
| Databáze: | OpenAIRE |
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