Mechanosensory channels mediate ER Ca2+ transients to trigger assembly of autophagosome initiation sites for degradation of ER subdomains - PubMed
21 hours ago
- #Calcium signaling
- #ER-phagy
- #Autophagosome assembly
- Stress conditions like prolonged starvation, cholesterol dyshomeostasis, and high-Ca²⁺ insults cause expansion of sheet ER subdomains with high luminal Ca²⁺, which are then degraded via ER-phagy.
- Autophagosome formation for ER sheet sequestration relies on FAM134B and lipidated LC3, while autophagy proteins ATG14 and ATG9 are partially dispensable.
- ER-localized mechanosensory channels PIEZO1 and TRPV1 are enriched at high-Ca²⁺ ER sheets, mediating Ca²⁺ transients that trigger liquid-liquid phase separation of the FIP200 complex to initiate ER-phagy.
- Membranes of autophagosomes enclosing high-Ca²⁺ ER sheets are directly remodeled from the ER, as shown by electron microscopy and cryo-electron tomography.
- Distinct mechanisms are used for forming autophagosomes that enclose high-Ca²⁺ ER subdomains versus non-selective autophagosomes.