ppGpp functions as an alarmone in metazoa

Doshun Ito, Hinata Kawamura, Akira Oikawa, Yuta Ihara, Toshio Shibata, Nobuhiro Nakamura, Tsunaki Asano, Shun Ichiro Kawabata, Takashi Suzuki, Shinji Masuda

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number671
JournalCommunications Biology
Volume3
Issue number1
DOIs
Publication statusPublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)
  • Medicine(all)

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