RT info:eu-repo/semantics/article T1 Functional roles of MICU1 and MICU2 in mitochondrial Ca 2+ uptake A1 Matesanz Isabel, Jessica A1 Arias del Val, Jessica A1 Álvarez Illera, María Pilar A1 Fonteriz García, Rosalba Inés A1 Montero, Mayte A1 Álvarez Martín, Javier AB MICU1 and MICU2 are the main regulators of the mitochondrial Ca(2+)-uniporter (MCU), but their precise functional role is still under debate. We show here that MICU2 behaves as a pure inhibitor of MCU at low cytosolic [Ca(2+)] ([Ca(2+)]c), though its effects decrease as [Ca(2+)]c is increased and disappear above 7 μM. Regarding MICU1, studying its effects is more difficult because knockdown of MICU1 leads also to loss of MICU2. However, while knockdown of MICU2 induces only a persistent increase in mitochondrial Ca(2+) uptake, knockdown of MICU1 also induces a peculiar use-dependent transient activation of MCU that cannot be attributed to the parallel loss of MICU2. Therefore, MICU1 is endowed with a specific inhibitory effect on MCU at low [Ca(2+)]c, separate and kinetically different from that of MICU2. On the other hand, we and others have shown previously that MICU1 activates MCU at [Ca(2+)]c above 2.5 μM. Thus, MICU1 has a double role in MCU regulation, inhibitory at low [Ca(2+)]c and activatory at high [Ca(2+)]c. SN 0005-2736 YR 2016 FD 2016 LK https://uvadoc.uva.es/handle/10324/73902 UL https://uvadoc.uva.es/handle/10324/73902 LA eng NO Matesanz-Isabel J, Arias-del-Val J, Alvarez-Illera P, Fonteriz RI, Montero M, Alvarez J. Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake. Biochim Biophys Acta. 2016 Jun;1858(6):1110-7. doi: 10.1016/j.bbamem.2016.02.022. Epub 2016 Feb 18. PMID: 26903221. NO Producción Científica DS UVaDOC RD 04-abr-2025