Tsukuba, Japan—Organisms survive while enduring various stresses such as temperature, ultraviolet radiation, and interspecies interactions. Within tolerable limits, they can survive by exhibiting resistance. Nevertheless, when they are subjected to excessive stress beyond their capacity (lethal stress), individuals die. The mechanisms that control such stress-dependent individual death have remained unclear.
The research team conducted experiments using the fruit fly Drosophila melanogaster and identified Phaedra1 ( Phae1 ) as a lethal stress-responsive gene that activates a protein essential for cell death in neurons and consequently induces individual death. Phae1 activates a protein required for cell death in neurons, resulting in the induction of individual death. Researchers also determined that Phae1 expression is regulated by the transcription factor Zeste. Moreover, when exploring compounds that affect Phae1 expression, they found that rapamycin, an inhibitor of the signaling factor mTOR, suppresses Phae1 expression. Specifically, neuronal-specific reduction of mTor function suppressed the expression of zeste and Phae1 and increased the survival rates after exposure to lethal stress. These findings suggest that the mTOR-Zeste-Phae1 pathway controls stress-induced individual death in D. melanogaster .
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This work was supported by JSPS KAKENHI (19J12272, 22KJ0339, 24K18156) grants to T.M., by a Promotion of Development of a Joint Usage/ Research System Project: Coalition of Universities for Research Excellence Program (CURE) from the MEXT (JPMXP1323015486) grant to A.N., and by support from the program of Joint Usage/Research Center for Developmental Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University (K24-15) to R.N.. T.M. was also a recipient of a JSPS Young Investigator fellowship.
Title of original paper:
Stress-induced organismal death is genetically regulated by the mTOR-Zeste-Phae1 axis
Journal:
Proceedings of the National Academy of Sciences
Assistant Professor MATSUMURA, Takashi
Professor NIWA, Ryusuke
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba
Professor Emeritus HAYAKAWA, Yoichi
Saga University
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
Proceedings of the National Academy of Sciences
Stress-induced organismal death is genetically regulated by the mTOR–Zeste–Phae1 axis
9-Sep-2025