| First Author | Singaravelu K | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 14 | Pages | 12189-201 |
| PubMed ID | 21220420 | Mgi Jnum | J:171160 |
| Mgi Id | MGI:4948806 | Doi | 10.1074/jbc.M110.174029 |
| Citation | Singaravelu K, et al. (2011) Mitofusin 2 Regulates STIM1 Migration from the Ca2+ Store to the Plasma Membrane in Cells with Depolarized Mitochondria. J Biol Chem 286(14):12189-201 |
| abstractText | Store-operated Ca(2+) channels in the plasma membrane (PM) are activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER) and constitute a widespread and highly conserved Ca(2+) influx pathway. After store emptying, the ER Ca(2+) sensor STIM1 forms multimers, which then migrate to ER-PM junctions where they activate the Ca(2+) release-activated Ca(2+) channel Orai1. Movement of an intracellular protein to such specialized sites where it gates an ion channel is without precedence, but the fundamental question of how STIM1 migrates remains unresolved. Here, we show that trafficking of STIM1 to ER-PM junctions and subsequent Ca(2+) release-activated Ca(2+) channel activity is impaired following mitochondrial depolarization. We identify the dynamin-related mitochondrial protein mitofusin 2, mutations of which causes the inherited neurodegenerative disease Charcot-Marie-Tooth IIa in humans, as an important component of this mechanism. Our results reveal a molecular mechanism whereby a mitochondrial fusion protein regulates protein trafficking across the endoplasmic reticulum and reveals a homeostatic mechanism whereby mitochondrial depolarization can inhibit store-operated Ca(2+) entry, thereby reducing cellular Ca(2+) overload. |
