STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria
STIM1 is a transmembrane protein localized in the endoplasmic reticulum (ER), where it acts as a calcium ion sensor, activating store-operated Ca2+ entry upon ER Ca2+ depletion. Via cellular calcium influx, STIM1 is thought to indirectly affect mitochondrial calcium content. Here we show that STIM1...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:dnet:digitalcsic_::3127757af8417bae696a1e1de6105fd0 |
| Acceso en línea: | http://hdl.handle.net/10261/429059 |
| Access Level: | acceso abierto |
| Palabra clave: | Calcium GRP75 MAM Mitochondria STIM1 |
| Sumario: | STIM1 is a transmembrane protein localized in the endoplasmic reticulum (ER), where it acts as a calcium ion sensor, activating store-operated Ca2+ entry upon ER Ca2+ depletion. Via cellular calcium influx, STIM1 is thought to indirectly affect mitochondrial calcium content. Here we show that STIM1 also interacts with mitochondrial proteins such as PTPIP51 and GRP75, suggesting its presence in mitochondria-associated ER membranes (MAMs), which are specialized ER regions that facilitate ER-mitochondria communication. Lowering STIM1 expression disrupts ER-to-mitochondria Ca2+ transfer, reduces basal mitochondrial Ca2+ levels, impairs maximal mitochondrial respiration, and reduces ATP production. The STIM1-GRP75 interaction depends on STIM1’s Ca2+-sensing ability. ER Ca2+ depletion or the constitutive-open R429C mutation both reduce STIM1 binding to GRP75, suggesting that conformational changes in STIM1 play a role in this interaction. Deletion analysis revealed that the STIM1 (551-611) segment is crucial for GRP75 binding, as the peptide STIM1(551-611) binds GRP75, while STIM1(Δ551-611) shows reduced binding. These findings reveal a previously unrecognized role of STIM1 in direct inter-organelle communication |
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