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Title

Functional roles of MICU1 and MICU2 in mitochondrial Ca2+ uptake

AuthorsMatesanz-Isabel, Jessica; Arias-del-Val, Jessica; Alvarez-Illera, Pilar; Fonteriz, Rosalba I. ; Montero, Mayte ; Álvarez, Javier
KeywordsMICU1
MICU2
Aequorin
HeLa cells
Calcium
MCU
Issue Date2016
PublisherElsevier
CitationBiochimica et Biophysica Acta - Biomembranes 1858(6): 1110-1117 (2016)
AbstractMICU1 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.
Publisher version (URL)https://doi.org/10.1016/j.bbamem.2016.02.022
URIhttp://hdl.handle.net/10261/157927
Identifiersdoi: 10.1016/j.bbamem.2016.02.022
issn: 0005-2736
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