ppGpp functions as an alarmone in metazoa

Doshun Ito1, Hinata Kawamura1, Akira Oikawa2

  • 1Department of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.

Communications Biology
|November 14, 2020
PubMed

Insights

Guanosine 3',5'-bis(pyrophosphate) (ppGpp) is detected in animal cells, revealing its role in the stringent response. ppGpp accumulation in Drosophila causes metabolic changes, cell death, and lethality, establishing its physiological relevance in animals.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Animal Physiology

Background:

  • Guanosine 3 ',5 '-bis(pyrophosphate) (ppGpp) is a bacterial second messenger regulating physiology.
  • Metazoan SpoT homolog-1 (Mesh1) hydrolase suggests a role for ppGpp in animals, but ppGpp itself has not been detected in animal cells.
  • The physiological relevance of ppGpp in metazoans remains unestablished due to its prior undetected status.

Purpose of the Study:

  • To detect ppGpp in animal cells (Drosophila and human).
  • To investigate the physiological effects of ppGpp accumulation in Drosophila.
  • To establish the existence and function of the ppGpp-dependent stringent response in animals.

Main Methods:

  • Detection of ppGpp in Drosophila and human cells.
  • Induction of ppGpp accumulation in Drosophila.
  • Observation of metabolic changes, cell death, and lethality in response to ppGpp.

Main Results:

  • ppGpp was successfully detected in both Drosophila and human cells.
  • ppGpp accumulation in Drosophila led to significant metabolic alterations.
  • Increased ppGpp levels resulted in cell death and eventual lethality in Drosophila.

Conclusions:

  • This study provides the first evidence for the detection of ppGpp in animal cells.
  • The findings demonstrate the functional role of ppGpp in inducing a stringent response in animals.
  • The results establish the physiological relevance and impact of ppGpp in metazoan organisms.

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