MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity

• DOI: 10.1016/j.molcel.2014.01.013
• Publication Date: 2014-02-20T14:00:50Z
• Authors: Maria Patron; Vanessa Checchetto; Anna Raffaello; Enrico Teardo; Denis Vecellio Reane; Maura Mantoan; Veronica Granatiero; Ildikò Szabò; Diego De Stefani; Rosario Rizzuto
• Keywords: Uniporter; Organelle

Mitochondrial calcium accumulation was recently shown to depend on a complex composed of an inner-membrane channel (MCU and MCUb) regulatory subunits (MICU1, MCUR1, EMRE). A fundamental property MCU is low activity at resting cytosolic Ca(2+) concentrations, preventing deleterious cycling organelle overload. Here we demonstrate that these properties are ensured by heterodimer two proteins with opposite effects, MICU1 MICU2, which, both in purified lipid bilayers intact cells, stimulate inhibit activity, respectively. Both MICU2 regulated through their EF-hand domains, thus accounting for the sigmoidal response [Ca(2+)] situ allowing tight physiological control. At [Ca(2+)], dominant effect largely shuts down activity; higher stimulatory allows prompt mitochondria signals generated cytoplasm.