Functional roles of MICU1 and MICU2 in mitochondrial Ca2+ uptake
MICU1 and MICU2 are the main regulators of the mitochondrial Ca2 +-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 [Ca2 +] ([Ca2 +]c), though its effects decrease as [Ca2 +]c is increased and disapp...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión enviada para evaluación y publicación |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/157927 |
| Acceso en línea: | http://hdl.handle.net/10261/157927 |
| Access Level: | acceso abierto |
| Palabra clave: | MICU1 MICU2 Aequorin HeLa cells Calcium MCU |
| Sumario: | MICU1 and MICU2 are the main regulators of the mitochondrial Ca2 +-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 [Ca2 +] ([Ca2 +]c), though its effects decrease as [Ca2 +]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 Ca2 + 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 [Ca2 +]c, separate and kinetically different from that of MICU2. On the other hand, we and others have shown previously that MICU1 activates MCU at [Ca2 +]c above 2.5 μM. Thus, MICU1 has a double role in MCU regulation, inhibitory at low [Ca2 +]c and activatory at high [Ca2 +]c. |
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