Parkin-dependent regulation of the MCU complex component MICU1

Scientific Reports
Alessandra MatteucciTito Calì

Abstract

The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by the Ca2+ selective pore-forming subunit, the mitochondrial uniporter (MCU), and accessory proteins, including MICU1, MICU2 and EMRE. Their concerted action is required to fine-tune the uptake of Ca2+ into the mitochondrial matrix which both sustains cell bioenergetics and regulates the apoptotic response. To adequately fulfil such requirements and avoid impairment in mitochondrial Ca2+ handling, the intracellular turnover of all the MCU components must be tightly regulated. Here we show that the MCU complex regulator MICU1, but not MCU and MICU2, is rapidly and selectively degraded by the Ubiquitin Proteasome System (UPS). Moreover, we show that the multifunctional E3 ubiquitin ligase Parkin (PARK2), whose mutations cause autosomal recessive early-onset Parkinson's disease (PD), is a potential candidate involved in this process since its upregulation strongly decreases the basal level of MICU1. Parkin was found to interact with MICU1 and, interestingly, Parkin Ubl-domain, but not its E3-ubquitin ligase activity, is required for the degradation of MICU1, suggesting that in addition to the well documented role in the control of Parkin basal auto-inhi...Continue Reading

References

Apr 1, 1990·Physiological Reviews·J G McCormackR M Denton
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·L S JouavilleR Rizzuto
May 29, 2000·The New England Journal of Medicine·C B LückingUNKNOWN European Consortium on Genetic Susceptibility in Parkinson's Disease
Feb 17, 2001·American Journal of Human Genetics·M PeriquetUNKNOWN French Parkinson's Disease Genetics Study Group. The European Consortium on Genetic Susceptibility in Parkinson's Disease
May 10, 2002·The American Journal of Pathology·Michael G SchlossmacherKenneth S Kosik
Feb 18, 2003·Human Molecular Genetics·Frédéric DariosAlexis Brice
Jun 24, 2004·Seminars in Cell & Developmental Biology·Rasmus Hartmann-Petersen, Colin Gordon
Jul 15, 2004·Proceedings of the National Academy of Sciences of the United States of America·Dongdong YaoStuart A Lipton
Dec 21, 2004·Journal of Neurochemistry·Iris H HennKonstanze F Winklhofer
May 1, 2007·Antioxidants & Redox Signaling·Hua-Qin WangRyosuke Takahashi
Jul 11, 2007·Current Opinion in Neurology·Christine Klein, Katja Lohmann-Hedrich
Nov 26, 2008·The Journal of Cell Biology·Derek NarendraRichard J Youle
Apr 3, 2009·The Journal of Biological Chemistry·Ventzislava A HristovaGary S Shaw
May 6, 2009·Biochimica Et Biophysica Acta·Richard M Denton
Jul 18, 2009·Journal of Neuroscience Research·Kenneth M RosenHenry W Querfurth
Oct 31, 2009·The Journal of Biological Chemistry·Susan S Safadi, Gary S Shaw
Jan 26, 2010·Nature Cell Biology·Sven GeislerWolfdieter Springer
Aug 10, 2010·Nature·Fabiana PerocchiVamsi K Mootha
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Han Seok KoTed M Dawson
Jun 23, 2011·The EMBO Journal·Viduth K ChauguleHelen Walden
Aug 2, 2012·Nature Reviews. Molecular Cell Biology·Rosario RizzutoCristina Mammucari
Mar 20, 2013·Molecular and Cellular Biology·Piotr BragoszewskiAgnieszka Chacinska
Jun 12, 2013·ELife·Dipayan ChaudhuriDavid E Clapham
Sep 14, 2013·Neuro-degenerative Diseases·Ted M Dawson, Valina L Dawson

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Citations

Apr 30, 2019·Cell Cycle·Saverio MarchiPaolo Pinton
Aug 2, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shaunrick StollHongyu Qiu
Oct 2, 2019·International Journal of Molecular Sciences·Nadezhda V TarasovaAndrey V Elchaninov
Sep 12, 2020·Cells·Enrico Zampese, D James Surmeier
Mar 11, 2020·International Journal of Molecular Sciences·Lucia BarazzuolTito Calì
Dec 10, 2020·American Journal of Physiology. Cell Physiology·B Rita AlevriadouMuniswamy Madesh
Nov 27, 2019·Trends in Molecular Medicine·Liron BoymanW Jonathan Lederer
Dec 24, 2019·Current Opinion in Chemical Biology·Joshua J Woods, Justin J Wilson
Feb 23, 2020·Mechanisms of Ageing and Development·Konstantinos Palikaras, Nektarios Tavernarakis
Jun 26, 2021·Frontiers in Aging Neuroscience·Luoan ShenChengmei Sun

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Methods Mentioned

BETA
ubiquitination
electrophoresis
co-immunoprecipitation
immunoprecipitation
pull down
transfection

Software Mentioned

GraphPad Prism
GraphPad
ImageJ

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