RT info:eu-repo/semantics/article
T1 MICU1 Controls Both the Threshold and Cooperative Activation of the Mitochondrial Ca2+ Uniporter
A1 Csordás, György
A1 Golenár, Tünde
A1 Seifert, Erin L.
A1 Kamer, Kimberli J.
A1 Sancak, Yasemin
A1 Perocchi, Fabiana
A1 Moffat, Cynthia
A1 Weaver, David
A1 Perez, Sergio de la Fuente
A1 Bogorad, Roman
A1 Koteliansky, Victor
A1 Adijanto, Jeffrey
A1 Mootha, Vamsi K.
A1 Hajnóczky, György
AB Mitochondrial Ca(2+) uptake via the uniporter is central to cell metabolism, signaling, and survival. Recent studies identified MCU as the uniporter's likely pore and MICU1, an EF-hand protein, as its critical regulator. How this complex decodes dynamic cytoplasmic [Ca(2+)] ([Ca(2+)]c) signals, to tune out small [Ca(2+)]c increases yet permit pulse transmission, remains unknown. We report that loss of MICU1 in mouse liver and cultured cells causes mitochondrial Ca(2+) accumulation during small [Ca(2+)]c elevations but an attenuated response to agonist-induced [Ca(2+)]c pulses. The latter reflects loss of positive cooperativity, likely via the EF-hands. MICU1 faces the intermembrane space and responds to [Ca(2+)]c changes. Prolonged MICU1 loss leads to an adaptive increase in matrix Ca(2+) binding, yet cells show impaired oxidative metabolism and sensitization to Ca(2+) overload. Collectively, the data indicate that MICU1 senses the [Ca(2+)]c to establish the uniporter's threshold and gain, thereby allowing mitochondria to properly decode different inputs.
PB Cell Press
SN 1550-4131
YR 2013
FD 2013-06-04
LK https://uvadoc.uva.es/handle/10324/70088
UL https://uvadoc.uva.es/handle/10324/70088
LA eng
NO Csordás G, Golenár T, Seifert EL, Kamer KJ, Sancak Y, Perocchi F, Moffat C, Weaver D, Perez SF, Bogorad R, Koteliansky V, Adijanto J, Mootha VK, Hajnóczky G. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca²⁺ uniporter. Cell Metab. 2013 Jun 4;17(6):976-987. doi: 10.1016/j.cmet.2013.04.020. PMID: 23747253; PMCID: PMC3722067.
NO Producción Científica
DS UVaDOC
RD 23-nov-2024