Show simple item record Melanie Paillard Csordás György Szanda Gergő Golenár Tünde Valentina Debattisti Bartók Ádám Nadan Wang Cynthia Moffat Erin L. Seifert Spät András Hajnóczky György 2018-10-05T07:03:11Z 2018-10-05T07:03:11Z 2017
dc.identifier 85014549297
dc.identifier.citation pagination=2291-2300; journalVolume=18; journalIssueNumber=10; journalTitle=CELL REPORTS;
dc.identifier.uri doi:10.1016/j.celrep.2017.02.032
dc.description.abstract Mitochondrial Ca2+ uptake through the Ca2+ uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca2+-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca2+] threshold for Ca2+ uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver. In MICU1-overexpressing cells, MICU1 was pulled down by MCU proportionally to MICU1 overexpression, suggesting that MICU1:MCU protein ratio directly reflected their association. Overexpressing MICU1 in the heart increased MICU1:MCU ratio, leading to liver-like mitochondrial Ca2+ uptake phenotype and cardiac contractile dysfunction. Thus, the proportion of MICU1-free and MICU1-associated MCU controls these tissue-specific uniporter phenotypes and downstream Ca2+ tuning of oxidative metabolism. © 2017
dc.relation.ispartof urn:issn:2211-1247
dc.title Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU
dc.type Journal Article 2018-02-19T11:50:52Z
dc.language.rfc3066 en
dc.identifier.mtmt 3201118

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