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In\n                    <jats:italic>Drosophila<\/jats:italic>\n                    gut enterocytes, we recently identified a novel form of cell death, termed erebosis. Erebosis is a nonapoptotic, nonautophagic, and nonnecrotic process, in which affected cells accumulate Ance (angiotensin-converting enzyme) and lose many other proteins, ultimately leading to the loss of organelles and the nucleus. The underlying molecular mechanism of erebosis has remained unclear. Here, through single-cell RNA sequencing and genetic approaches, we found that the small metabolite heme regulates erebosis. Cells undergoing erebosis up-regulate the heme-degrading enzyme\n                    <jats:italic>Heme oxygenase (Ho)<\/jats:italic>\n                    and the heme exporter\n                    <jats:italic>Mrp5<\/jats:italic>\n                    , and decrease intracellular amounts of heme. Heme depletion by\n                    <jats:italic>Mrp5<\/jats:italic>\n                    overexpression promotes erebosis, whereas heme accumulation by knockdown of\n                    <jats:italic>Ho<\/jats:italic>\n                    or\n                    <jats:italic>Mrp5<\/jats:italic>\n                    , or by feeding a heme precursor, suppresses it. Downstream of heme, Dpp signaling suppresses erebosis. Inhibition of erebosis reduces intestinal stem cell proliferation, indicating a cross-talk mechanism between enterocyte death and stem cell division. Our results demonstrate that reduction of cytoplasmic heme is a critical step in initiating enterocyte erebosis and coordinating stem cell proliferation, thereby maintaining gut tissue homeostasis. This work provides the first insight into the molecular mechanism regulating erebosis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003942","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:25:31Z","timestamp":1787160331000},"page":"e3003942","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heme acts as a metabolic brake on erebosis in the Drosophila 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