2026-04-03 中国科学院（CAS）
Model of autophagosome formation containing high-Ca²⁺ ER (Image by ZHANG Hong’s group)
＜関連情報＞
- https://english.cas.cn/newsroom/research-news/202604/t20260403_1155101.shtml
- https://www.cell.com/molecular-cell/abstract/S1097-2765(26)00158-9
機械受容チャネルはER Ca 2+の一過性変化を媒介し、ERサブドメインの分解のためのオートファゴソーム開始部位の形成を誘発する Mechanosensory channels mediate ER Ca2+ transients to trigger assembly of autophagosome initiation sites for degradation of ER subdomains
Xiaoli Ma ∙ Zhiyang Cheng ∙ Hongyu Zhao ∙ … ∙ Qiaoxia Zheng ∙ Wei Ji ∙ Hong Zhang
Molecular Cell Published: April 2, 2026
DOI:https://doi.org/10.1016/j.molcel.2026.03.002
Highlights
- Stress-induced, Ca²⁺-enriched ER sheets are selectively degraded by autophagy
- FAM134B and lipidated LC3 mediate autophagic degradation of Ca²⁺-enriched ER sheets
- PIEZO1 and TRPV1 mediate Ca²⁺ transients to trigger FIP200 punctum formation
- ER-phagy maintains ER Ca2+ homeostasis
Summary
ER-phagy involves the selective autophagosomal engulfment of ER fragments, but the signaling events, selection mechanisms, and membrane source of ER-phagic autophagosomes remain elusive. Here, using state-of-the-art super-resolution multi-SIM imaging, we reveal that stresses (prolonged starvation, cholesterol dyshomeostasis, and high-Ca2+ insults) trigger the expansion of sheet ER subdomains containing high levels of luminal Ca2+ in mammalian cells, which are subsequently degraded by ER-phagy. Autophagosome formation and sequestration of ER sheets require the concerted actions of FAM134B and lipidated LC3, whereas the autophagy proteins ATG14 and ATG9 are partially dispensable. Electron microscopy and cryo-electron tomography show that the membranes of autophagosomes enclosing high-Ca2+-containing ER sheets are directly remodeled from the ER. The ER-localized cation channels PIEZO1 and TRPV1 are enriched at and mediate Ca2+ transients from high-Ca2+-containing ER sheets, triggering liquid-liquid phase separation of the autophagosome-initiating FIP200 complex to initiate ER-phagy. Thus, distinct mechanisms are employed for the formation of high-Ca2+-containing ER-enclosing autophagosomes and non-selective autophagosomes.
