Parallel enterocyte caspase and cytokine responses couple hypoxia to reoxygenation-dependent intestinal regeneration in Drosophila

Hypoxia primes adult Drosophila enterocytes for apoptosis and activates Upd/JAK-STAT signaling in ISCs, but damage and proliferation only occur after reoxygenation.

• Why it matters: Oxygen fluctuations in the intestine are common in health and disease, yet the timing and coordination of epithelial damage versus regeneration under hypoxia–reoxygenation are unclear.
• What they did: In adult Drosophila intestine, hypoxia triggers an AMPK-p53-dependent enterocyte program and a separate Upd cytokine response that activates JAK-STAT in ISCs; apoptosis and ISC proliferation are then assessed across oxygen restoration.
• The result: After reoxygenation, enterocyte loss and ISC proliferation proceed together and are required to recover intestinal length; HIF-1/Sima is dispensable in enterocytes but required in progenitor cells, and repeated hypoxia–reoxygenation shortens lifespan, worsened by enterocyte p53 knockdown.

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