PUBLICATION
Sirt1 promotes tissue regeneration in zebrafish through regulating the mitochondrial unfolded protein response
- Authors
- Lin, Y.F., Sam, J., Evans, T.
- ID
- ZDB-PUB-211009-2
- Date
- 2021
- Source
- iScience 24: 103118 (Journal)
- Registered Authors
- Evans, Todd
- Keywords
- Cell biology, Developmental biology, Molecular biology
- Datasets
- GEO:GSE182113
- MeSH Terms
- none
- PubMed
- 34622167 Full text @ iScience
Citation
Lin, Y.F., Sam, J., Evans, T. (2021) Sirt1 promotes tissue regeneration in zebrafish through regulating the mitochondrial unfolded protein response. iScience. 24:103118.
Abstract
The mitochondrial unfolded protein response (UPRmt) is an organellar stress signaling pathway that functions to detect and restore disruption of mitochondrial proteostasis. The UPRmt is involved in a wide range of physiological and disease conditions, including aging, stem cell maintenance, innate immunity, neurodegeneration, and cancer. Here we report that the UPRmt is integral to zebrafish fin regeneration. Taking advantage of a novel zebrafish UPRmt reporter, we observed that UPRmt activation occurs in regenerating fin tissue shortly after injury. Through chemical and genetic approaches, we discovered that the Sirt1-UPRmt pathway, best known for its role in promoting lifespan extension, is crucial for fin regeneration. The metabolism of NAD+ is an important contributor to Sirt1 activity in this context. We propose that Sirt1 activation induces mitochondrial biogenesis in injured fin tissue, which leads to UPRmt activation and promotes tissue regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping