CCN6 regulates mitochondrial respiratory complex assembly and activity.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Deepesh Kumar PadhanMalini Sen

Abstract

Cellular communication network factor 6 (CCN6) mutations are linked with Progressive Pseudo Rheumatoid Dysplasia (PPRD) a debilitating musculoskeletal disorder. The function of CCN6 and the mechanism of PPRD pathogenesis remain unclear. Accordingly, we focused on the functional characterization of CCN6 and CCN6 mutants. Using size exclusion chromatography and native polyacrylamide gel electrophoresis we demonstrated that CCN6 is present as a component of the mitochondrial respiratory complex in human chondrocyte lines. By means of siRNA-mediated transfection and electron microscopy we showed that moderate reduction in CCN6 expression decreases the RER- mitochondria inter-membrane distance. Parallel native PAGE, immunoblotting and Complex I activity assays furthermore revealed increase in both mitochondrial distribution of CCN6 and mitochondrial respiratory complex assembly/activity in CCN6 depleted cells. CCN6 mutants resembling those linked with PPRD, which were generated by CRISPR-Cas9 technology displayed low level of expression of mutant CCN6 protein and inhibited respiratory complex assembly/activity. Electron microscopy and MTT assay of the mutants revealed abnormal mitochondria and poor cell viability. Taken together, ou...Continue Reading

References

Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·D PennicaA J Levine
Jan 28, 2003·Journal of Cellular Physiology·Masaharu TakigawaTakashi Nishida
Feb 12, 2004·Arthritis and Rheumatism·Malini SenDennis A Carson
Apr 20, 2004·The International Journal of Biochemistry & Cell Biology·Jürgen Engel
Feb 17, 2006·Biochemical and Biophysical Research Communications·Leila DavisMalini Sen
Sep 20, 2006·The Journal of Cell Biology·György CsordásGyörgy Hajnóczky
Feb 9, 2007·Biochemical and Biophysical Research Communications·Dustyn S Miller, Malini Sen
Apr 5, 2007·Nature Protocols·Ilka WittigHermann Schägger
Sep 16, 2008·Trends in Biochemical Sciences·Kenneth P HolbournBernard Perbal
Nov 26, 2008·Molecular Cell·Rebeca Acín-PérezJose Antonio Enriquez
Jan 9, 2009·Development, Growth & Differentiation·Ken-ichi KatsubeAkira Yamaguchi
Oct 10, 2009·Nature Protocols·Mariusz R WieckowskiPaolo Pinton
Aug 19, 2010·The EMBO Journal·Olga Martins de Brito, Luca Scorrano
Apr 26, 2011·Methods in Molecular Biology·Johan van MeerlooJacqueline Cloos
Sep 20, 2011·Biochimica Et Biophysica Acta·Masakazu MimakiMichael T Ryan
Feb 22, 2012·Cell Metabolism·David Moreno-LastresCristina Ugalde
Jul 14, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Nuria Garcia SegarraLuisa Bonafé
Sep 19, 2012·American Journal of Medical Genetics. Part a·Ashwin DalalK M Girisha
Feb 20, 2013·Journal of Cell Communication and Signaling·Bernard Perbal
Feb 21, 2013·Journal of Cell Science·Srinivasa Rao RepudiMalini Sen
Sep 10, 2013·Methods in Enzymology·Cheryl M Koh
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
May 28, 2014·Nucleic Acids Research·Tessa G MontagueEivind Valen
Mar 27, 2016·Journal of Neurochemistry·Balaraju SunithaMuchukunte Mukunda Srinivas Bharath
Jun 3, 2016·Journal of Cell Science·Milan PatraMalini Sen
Aug 11, 2016·Scientific Reports·Amy E VincentMartin Picard
Apr 6, 2017·Cell Metabolism·Dusanka MilenkovicJudy Hirst
Nov 3, 2017·Cold Spring Harbor Molecular Case Studies·M Reza SailaniMichael P Snyder
Dec 21, 2017·Cold Spring Harbor Molecular Case Studies·Salem AlawbathaniSebahattin Cirak
Apr 13, 2019·Nucleic Acids Research·Fábio MadeiraRodrigo Lopez
Jun 22, 2019·Cell Stress·David Pacheu-GrauMarkus Deckers

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Citations

Mar 2, 2021·Frontiers in Cell and Developmental Biology·Archya SenguptaMalini Sen

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