TY - JOUR
T1 - ppGpp functions as an alarmone in metazoa
AU - Ito, Doshun
AU - Kawamura, Hinata
AU - Oikawa, Akira
AU - Ihara, Yuta
AU - Shibata, Toshio
AU - Nakamura, Nobuhiro
AU - Asano, Tsunaki
AU - Kawabata, Shun Ichiro
AU - Suzuki, Takashi
AU - Masuda, Shinji
N1 - Funding Information:
We thank J. Chung (Seoul National University) for proving fly strains. We acknowledge support from JSPS KAKENHI Grant Number 19K22418 (to S.M.). D.I. is supported by a Grant-in-Aid for JSPS Fellows Grant Number 18J12607.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Guanosine 3′,5′-bis(pyrophosphate) (ppGpp) functions as a second messenger in bacteria to adjust their physiology in response to environmental changes. In recent years, the ppGpp-specific hydrolase, metazoan SpoT homolog-1 (Mesh1), was shown to have important roles for growth under nutrient deficiency in Drosophila melanogaster. Curiously, however, ppGpp has never been detected in animal cells, and therefore the physiological relevance of this molecule, if any, in metazoans has not been established. Here, we report the detection of ppGpp in Drosophila and human cells and demonstrate that ppGpp accumulation induces metabolic changes, cell death, and eventually lethality in Drosophila. Our results provide the evidence of the existence and function of the ppGpp-dependent stringent response in animals.
AB - Guanosine 3′,5′-bis(pyrophosphate) (ppGpp) functions as a second messenger in bacteria to adjust their physiology in response to environmental changes. In recent years, the ppGpp-specific hydrolase, metazoan SpoT homolog-1 (Mesh1), was shown to have important roles for growth under nutrient deficiency in Drosophila melanogaster. Curiously, however, ppGpp has never been detected in animal cells, and therefore the physiological relevance of this molecule, if any, in metazoans has not been established. Here, we report the detection of ppGpp in Drosophila and human cells and demonstrate that ppGpp accumulation induces metabolic changes, cell death, and eventually lethality in Drosophila. Our results provide the evidence of the existence and function of the ppGpp-dependent stringent response in animals.
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U2 - 10.1038/s42003-020-01368-4
DO - 10.1038/s42003-020-01368-4
M3 - Article
C2 - 33188280
AN - SCOPUS:85095935790
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 671
ER -