2026-08-26 理化学研究所,神戸大学
腸細胞のエレボーシス（黒い細胞）を抑制するヘム
＜関連情報＞
- https://www.riken.jp/press/2026/20260826_2/index.html
- https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003942
ヘムはショウジョウバエの腸管におけるエレボシスの代謝ブレーキとして機能する Heme acts as a metabolic brake on erebosis in the Drosophila gut
Motohiro Morikawa,Tetsutaro Hayashi,Yuko Ikegawa,Tomomi Takano,Kazuya Wata,Hirohisa Kyogoku,Mariko Kuse,Mika Yoshimura,Hiroshi Nishida,Rahul Parit,Dao My Linh,Kanta Kawai,Tasuku Hirayama, [ … ],Sa Kan Yoo
PLOS Biology Published: August 19, 2026
DOI:https://doi.org/10.1371/journal.pbio.3003942
Abstract
Tissue homeostasis relies on the balance between proliferation of stem cells and death of differentiated cells. In Drosophila 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 Heme oxygenase (Ho) and the heme exporter Mrp5, and decrease intracellular amounts of heme. Heme depletion by Mrp5 overexpression promotes erebosis, whereas heme accumulation by knockdown of Ho or Mrp5, 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.
