eLife (Apr 2018)

A genetic program mediates cold-warming response and promotes stress-induced phenoptosis in C. elegans

  • Wei Jiang,
  • Yuehua Wei,
  • Yong Long,
  • Arthur Owen,
  • Bingying Wang,
  • Xuebing Wu,
  • Shuo Luo,
  • Yongjun Dang,
  • Dengke K Ma

Journal volume & issue
Vol. 7


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How multicellular organisms respond to and are impacted by severe hypothermic stress is largely unknown. From C. elegans screens for mutants abnormally responding to cold-warming stimuli, we identify a molecular genetic pathway comprising ISY-1, a conserved uncharacterized protein, and ZIP-10, a bZIP-type transcription factor. ISY-1 gatekeeps the ZIP-10 transcriptional program by regulating the microRNA mir-60. Downstream of ISY-1 and mir-60, zip-10 levels rapidly and specifically increase upon transient cold-warming exposure. Prolonged zip-10 up-regulation induces several protease-encoding genes and promotes stress-induced organismic death, or phenoptosis, of C. elegans. zip-10 deficiency confers enhanced resistance to prolonged cold-warming stress, more prominently in adults than larvae. We conclude that the ZIP-10 genetic program mediates cold-warming response and may have evolved to promote wild-population kin selection under resource-limiting and thermal stress conditions.