title: Mitochondrial Ca(2+) uniporter (MCU)-dependent and MCU-independent Ca(2+) channels coexist in the inner mitochondrial membrane.
abstract: A protein referred to as CCDC109A and then renamed to mitochondrial calcium uniporter (MCU) has recently been shown to accomplish mitochondrial Ca(2+) uptake in different cell types. In this study, we investigated whole-mitoplast inward cation currents and single Ca(2+) channel activities in mitoplasts prepared from stable MCU knockdown HeLa cells using the patch-clamp technique. In whole-mitoplast configuration, diminution of MCU considerably reduced inward Ca(2+) and Na(+) currents. This was accompanied by a decrease in occurrence of single channel activity of the intermediate conductance mitochondrial Ca(2+) current (i-MCC). However, ablation of MCU yielded a compensatory 2.3-fold elevation in the occurrence of the extra large conductance mitochondrial Ca(2+) current (xl-MCC), while the occurrence of bursting currents (b-MCC) remained unaltered. These data reveal i-MCC as MCU-dependent current while xl-MCC and b-MCC seem to be rather MCU-independent, thus, pointing to the engagement of at least two molecularly distinct mitochondrial Ca(2+) channels.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, 8010, Graz, Austria.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Bondarenko
authors.forename: Claire
authors.initials: C
authors.lastname: Jean-Quartier
authors.forename: Warisara
authors.initials: W
authors.lastname: Parichatikanond
authors.forename: Muhammad Rizwan
authors.initials: MR
authors.lastname: Alam
authors.forename: Markus
authors.initials: M
authors.lastname: Waldeck-Weiermair
authors.forename: Roland
authors.initials: R
authors.lastname: Malli
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
mesh_terms: D000200:Action Potentials; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D051336:Mitochondrial Membranes / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C034703:mitochondrial calcium uniporter; D012964:Sodium; D002118:Calcium