Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex
Ming-Feng Tsai,Charles B Phillips,Matthew J. Ranaghan,Chen-Wei Tsai,Yujiao Wu,Carole Willliams,Christopher Miller +6 more
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TLDR
A second function of EMRE is revealed: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail, ensuring that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca2+ landscape.Abstract:
Mitochondrial Ca(2+) uptake, a process crucial for bioenergetics and Ca(2+) signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca(2+)-activated Ca(2+) channel, with the Ca(2+) pore formed by the MCU protein and Ca(2+)-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca(2+) permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca(2+) landscape.read more
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The machineries, regulation and cellular functions of mitochondrial calcium.
TL;DR: Expanding the understanding of the mechanisms of mitochondrial Ca2+ regulation and function in different cell types is an important task in biomedical research, which offers the possibility of targeting mitochondrial Ca 2+ machinery for the treatment of several disorders.
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Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes.
TL;DR: In this review, recent discoveries on the regulation of interorganellar Ca2+ homeostasis and its role in pathophysiology are summarized.
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Role of Cardiolipin in Mitochondrial Signaling Pathways.
TL;DR: The role of CL in cellular signaling pathways is summarized and focus on tissues with high-energy demand, like the heart, and the signaling pathways described here may play a general role in pathology.
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Mitochondrial Ca2+ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity
Zhiwei Dong,Santhanam Shanmughapriya,Dhanendra Tomar,Naveed Siddiqui,Solomon Lynch,Neeharika Nemani,Sarah L. Breves,Xue-Qian Zhang,Aparna Tripathi,Palaniappan Palaniappan,Massimo F. Riitano,Alison M. Worth,Ajay Seelam,Edmund Carvalho,Ramasamy Subbiah,Fabián Jaña,Jonathan Soboloff,Yizhi Peng,Joseph Y. Cheung,Suresh K. Joseph,Jeffrey L. Caplan,Sudarsan Rajan,Peter B. Stathopulos,Muniswamy Madesh +23 more
TL;DR: Both oxidation and mutation of MCU Cys-97 exhibited persistent MCU channel activity with higher [Ca2+]m uptake rate, elevated mROS, and enhanced [Ca1-m overload-induced cell death, and these effects were largely independent ofMCU interaction with its regulators.
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The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria
Tim König,Simon E. Tröder,Kavya Bakka,Anne Korwitz,Ricarda Richter-Dennerlein,Philipp A Lampe,Maria Patron,Mareike Mühlmeister,Sergio Guerrero-Castillo,Ulrich Brandt,Thorsten Decker,Ines Lauria,Angela Paggio,Rosario Rizzuto,Elena I. Rugarli,Diego De Stefani,Thomas Langer,Thomas Langer +17 more
TL;DR: The neuronal interactome of m-AAA proteases in mice is determined and a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca2+ uniporter MCU, is identified.
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Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
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