Mitochondrial Ca2+ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity

Molecular Cell
Zhiwei DongMuniswamy Madesh


Ca2+dynamics and oxidative signaling are fundamental mechanisms for mitochondrial bioenergetics and cell function. The MCU complex is the major pathway by which these signals are integrated in mitochondria. Whether and how these coactive elements interact with MCU have not been established. As an approach toward understanding the regulation of MCU channel by oxidative milieu, we adapted inflammatory and hypoxia models. We identified the conserved cysteine 97 (Cys-97) to be the only reactive thiol in human MCU that undergoes S-glutathionylation. Furthermore, biochemical, structural, and superresolution imaging analysis revealed that MCU oxidation promotes MCU higher order oligomer formation. Both oxidation and mutation of MCU Cys-97 exhibited persistent MCU channel activity with higher [Ca2+]muptake rate, elevated mROS, and enhanced [Ca2+]moverload-induced cell death. In contrast, these effects were largely independent of MCU interaction with its regulators. These findings reveal a distinct functional role for Cys-97 in ROS sensing and regulation of MCU activity.

Associated Datasets

Jan 12, 2017·Madesh Muniswamy


Mar 17, 2018·Genes·Corina T Madreiter-SokolowskiWolfgang F Graier
Mar 22, 2018·International Journal of Molecular Sciences·Germano GuerraFrancesco Moccia
Mar 20, 2018·Cell Death & Disease·Kalimuthusamy NatarajaseenivasanDianne Langford
Dec 15, 2017·Journal of the Royal Society, Interface·B Rita AlevriadouMuniswamy Madesh
Apr 9, 2018·Journal of the American Heart Association·An XieSamuel C Dudley
Nov 10, 2018·Methods and Applications in Fluorescence·Florian BaumgartGerhard J Schütz
Apr 30, 2019·Cell Cycle·Saverio MarchiPaolo Pinton
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexander G BickChristine E Seidman
Aug 21, 2019·Nature Communications·Benjamin GottschalkWolfgang F Graier
Oct 31, 2019·Channels·Jie Yu, Junsheng Yang
Oct 4, 2019·Antioxidants & Redox Signaling·Hsin Yao ChiuReshma Taneja
Jan 16, 2020·Biomolecules·Petr JežekLydie Plecitá-Hlavatá
Feb 16, 2020·Cells·Céline DelierneuxNadine Hempel
Feb 26, 2020·Expert Opinion on Therapeutic Targets·Jonathan P LambertJohn W Elrod
Dec 11, 2019·Cell Death and Differentiation·Yohan SantinJeanne Mialet-Perez
May 24, 2020·Basic Research in Cardiology·Shanna HamiltonDmitry Terentyev
Jul 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hawasatu DumbuyaElena Oancea
Sep 11, 2019·Nature Neuroscience·Caroline FecherThomas Misgeld
Jan 13, 2018·International Journal of Molecular Sciences·Francesco Moccia
Jan 3, 2018·FEBS Letters·Plamena R Angelova, Andrey Y Abramov
Jul 28, 2018·Cellular and Molecular Life Sciences : CMLS·Adam Horn, Jyoti K Jaiswal
Aug 31, 2018·Nature Communications·Santhanam ShanmughapriyaMuniswamy Madesh
Oct 19, 2018·Frontiers in Cellular Neuroscience·Rosella AbetiPaola Giunti
Jan 16, 2019·International Journal of Molecular Sciences·Qi-Tong Lin, Peter B Stathopulos
Jul 16, 2019·The EMBO Journal·Xin ZhangIvan Bogeski
Oct 2, 2019·International Journal of Molecular Sciences·Nadezhda V TarasovaAndrey V Elchaninov
Jan 25, 2020·Cell Death & Disease·Jeanne Mialet-Perez, Angelo Parini
Apr 23, 2020·Science Signaling·Neeharika NemaniMuniswamy Madesh
Oct 17, 2017·Frontiers in Cell and Developmental Biology·Jan Dudek
Mar 27, 2019·Oxidative Medicine and Cellular Longevity·Zhong-Jie LiuShi-Yuan Xu
Sep 21, 2018·Frontiers in Cell and Developmental Biology·Mariafrancesca ScaliseCesare Indiveri
Aug 26, 2018·Nature Reviews. Molecular Cell Biology·Carlotta GiorgiPaolo Pinton
Dec 18, 2018·F1000Research·Giorgia PallafacchinaRosario Rizzuto
Oct 30, 2019·The FEBS Journal·Corina T Madreiter-SokolowskiWolfgang F Graier

Related Concepts

Histamine Measurement
Establishment and Maintenance of Localization
Channel Activity
COX8A gene
Biochemical Pathway
Calcium [EPC]
Fast Protein Liquid Chromatography

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