Mechanisms of ion selectivity and throughput in the mitochondrial calcium uniporter Journal Article

   

Authors:	Delgado, B. D.; Long, S. B.
Article Title:	Mechanisms of ion selectivity and throughput in the mitochondrial calcium uniporter
Abstract:	The mitochondrial calcium uniporter, which regulates aerobic metabolism by catalyzing mitochondrial Ca2+ influx, is arguably the most selective ion channel known. The mechanisms for this exquisite Ca2+ selectivity have not been defined. Here, using a reconstituted system, we study the electrical properties of the channel's minimal Ca2+-conducting complex, MCU-EMRE, from Tribolium castaneum to probe ion selectivity mechanisms. The wild-type TcMCU-EMRE complex recapitulates hallmark electrophysiological properties of endogenous Uniporter channels. Through interrogation of pore-lining mutants, we find that a ring of glutamate residues, the "Elocus,"serves as the channel's selectivity filter. Unexpectedly, a nearby "D-locus"at the mouth of the pore has diminutive influence on selectivity. Anomalous mole fraction effects indicate that multiple Ca2+ ions are accommodated within the E-locus. By facilitating ion-ion interactions, the E-locus engenders both exquisite Ca2+ selectivity and high ion throughput. Direct comparison with structural information yields the basis for selective Ca2+ conduction by the channel. © 2022 The Authors.
Keywords:	calcium; wild types; mitochondria; electrophysiology; potassium; ion channel; ions; ion selectivity; electrophysiological properties; ca2+ influx; a-rings; channel selectivity; conducting complexes; mitochondrial calcium uniporter; probe ions
Journal Title:	Science Advances
Volume:	8
Issue:	50
ISSN:	2375-2548
Publisher:	Amer Assoc Advancement Science
Date Published:	2022-12-14
Start Page:	eade1516
Language:	English
DOI:	10.1126/sciadv.ade1516
PUBMED:	36525497
PROVIDER:	scopus
PMCID:	PMC9757755
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144207313&doi=10.1126%2fsciadv.ade1516&partnerID=40&md5=a798a1dce16dbe7dda81f51fa7fae8ff
Notes:	Article -- Export Date: 3 January 2023 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/201842