Abstract
Mitochondrial Ca2+ uptake is central to cell metabolism, signaling and survival. Recent studies identified MCU as the pore of the mitochondrial Ca2+ uniporter and MICU1 as its critical regulator. MICU1 and its paralogs, MICU2 and MICU3 are EF-hand proteins and are the primary candidates to confer Ca2+ sensitivity to the Ca2+ uniporter. We will present studies of the molecular mechanisms of the MICU-dependent closure of the uniporter at low [Ca2+] levels and its cooperative activation when [Ca2+] increases. Furthermore, we will present clues to the MICU-dependence of the tissue specific mitochondrial Ca2+ uptake profiles.
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