PUBLICATION

In vivo real-time ATP imaging in zebrafish hearts reveals G0s2 induces ischemic tolerance

Authors
Kioka, H., Kato, H., Fujita, T., Asano, Y., Shintani, Y., Yamazaki, S., Tsukamoto, O., Imamura, H., Kogo, M., Kitakaze, M., Sakata, Y., Takashima, S.
ID
ZDB-PUB-200110-8
Date
2020
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   34(2): 2041-2054 (Journal)
Registered Authors
Keywords
ATP, FRET, energy metabolism, in vivo imaging, ischemic tolerance
MeSH Terms
  • Fluorescence Resonance Energy Transfer*
  • Oxidative Phosphorylation
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Animals, Genetically Modified
  • Zebrafish/metabolism*
  • Myocardium*/metabolism
  • Myocardium*/pathology
  • Cell Cycle Proteins*/genetics
  • Cell Cycle Proteins*/metabolism
  • Animals
  • Myocardial Ischemia*/genetics
  • Myocardial Ischemia*/metabolism
  • Myocardial Ischemia*/pathology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
(all 16)
PubMed
31916304 Full text @ FASEB J.
Abstract
Most eukaryotic cells generate adenosine triphosphate (ATP) through the oxidative phosphorylation system (OXPHOS) to support cellular activities. In cultured cell-based experiments, we recently identified the hypoxia-inducible protein G0/G1 switch gene 2 (G0s2) as a positive regulator of OXPHOS, and showed that G0s2 protects cultured cardiomyocytes from hypoxia. In this study, we examined the in vivo protective role of G0s2 against hypoxia by generating both loss-of-function and gain-of-function models of g0s2 in zebrafish. Zebrafish harboring transcription activator-like effector nuclease (TALEN)-mediated knockout of g0s2 lost hypoxic tolerance. Conversely, cardiomyocyte-specific transgenic zebrafish hearts exhibited strong tolerance against hypoxia. To clarify the mechanism by which G0s2 protects cardiac function under hypoxia, we introduced a mitochondrially targeted FRET-based ATP biosensor into zebrafish heart to visualize ATP dynamics in in vivo beating hearts. In addition, we employed a mosaic overexpression model of g0s2 to compare the contraction and ATP dynamics between g0s2-expressing and non-expressing cardiomyocytes, side-by-side within the same heart. These techniques revealed that g0s2-expressing cardiomyocyte populations exhibited preserved contractility coupled with maintained intra-mitochondrial ATP concentrations even under hypoxic condition. Collectively, these results demonstrate that G0s2 provides ischemic tolerance in vivo by maintaining ATP production, and therefore represents a promising therapeutic target for hypoxia-related diseases.
Genes / Markers
Figures
No images available
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTcontrolDay 5
WThypoxiaDay 5
WThypoxiaDay 5
WThypoxiaDay 5
WThypoxiaDay 5
g0s2zf3282/+controlDay 5
g0s2zf3282/+hypoxiaDay 5
g0s2zf3282/zf3282controlDay 5
g0s2zf3282/zf3282hypoxiaDay 5
g0s2zf3282/zf3282hypoxiaDay 5
1 - 10 of 15
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nkhspGFF3AEtTransgenic Insertion
    zf3280TgTransgenic Insertion
      zf3281TgTransgenic Insertion
        zf3282
          		Small Deletion
          zf3446TgTransgenic Insertion
            1 - 5 of 5
            Show
            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            g0s2TALEN1-g0s2TALEN
            1 - 1 of 1
            Show
            Fish
            Fish
            g0s2zf3282/+
            g0s2zf3282/zf3282
            nkhspGFF3AEt; zf3281Tg
            WT
            zf3280Tg
            zf3446Tg
            1 - 6 of 6
            Show
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            CFPEFGCFP
            GAL4FFEFGGAL4FF
            mCherryEFGmCherry
            VenusEFGVenus
            1 - 4 of 4
            Show
            Mapping
            Your Input Welcome
            We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
            Citation
            Kioka, H., Kato, H., Fujita, T., Asano, Y., Shintani, Y., Yamazaki, S., Tsukamoto, O., Imamura, H., Kogo, M., Kitakaze, M., Sakata, Y., Takashima, S. (2020) In vivo real-time ATP imaging in zebrafish hearts reveals G0s2 induces ischemic tolerance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 34(2):2041-2054.