2026-04-23T21:10:38Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/700882025-09-05T11:43:27Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Csordás, György Golenár, Tünde Seifert, Erin L. Kamer, Kimberli J. Sancak, Yasemin Perocchi, Fabiana Moffat, Cynthia Weaver, David Fuente Pérez, Sergio De La Bogorad, Roman Koteliansky, Victor Adijanto, Jeffrey Mootha, Vamsi K. Hajnóczky, György 2013 Producción Científica 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. application/pdf https://uvadoc.uva.es/handle/10324/70088 eng Cell Press MICU1 Controls Both the Threshold and Cooperative Activation of the Mitochondrial Ca2+ Uniporter info:eu-repo/semantics/article TEXT UVaDOC. Repositorio Documental de la Universidad de Valladolid Hispana