N ‐acetyl‐ l ‐tyrosine is an intrinsic triggering factor of mitohormesis in stressed animals
| Autor: | Yoichi Hayakawa, Keiji Tajiri, Outa Uryu, Hitoshi Matsumoto, Fumikazu Matsuhisa, Takashi Matsumura |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system
NF-E2-Related Factor 2 Endogeny Mitochondrion Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Hemolymph Gene expression Genetics Animals News & Views Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Kelch-Like ECH-Associated Protein 1 Intrinsic factor Chemistry fungi Hormesis KEAP1 Mitochondria Cell biology body regions Tyrosine Reactive Oxygen Species 030217 neurology & neurosurgery |
| Zdroj: | EMBO Rep |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201949211 |
| Popis: | Under stress conditions, mitochondria release low levels of reactive oxygen species (ROS), which triggers a cytoprotective response, called "mitohormesis". It still remains unclear how mitochondria respond to stress-derived stimuli and release a low level of ROS. Here, we show that N-acetyl-l-tyrosine (NAT) functions as a plausible intrinsic factor responsible for these tasks in stressed animals. NAT is present in the blood or hemolymph of healthy animals, and its concentrations increase in response to heat stress. Pretreatment with NAT significantly increases the stress tolerance of tested insects and mice. Analyses using Drosophila larvae and cultured cells demonstrate that the hormetic effects are triggered by transient NAT-induced perturbation of mitochondria, which causes a small increase in ROS production and leads to sequential retrograde responses: NAT-dependent FoxO activation increases in the gene expression of antioxidant enzymes and Keap1. Moreover, we find that NAT represses tumor growth, possibly via the activation of Keap1. In sum, we propose that NAT is a vital endogenous molecule that could serve as a triggering factor for mitohormesis. |
| Databáze: | OpenAIRE |
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