NRIP1/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome

Human Molecular Genetics
Antonella IzzoLucio Nitsch


Mitochondrial dysfunction, which is consistently observed in Down syndrome (DS) cells and tissues, might contribute to the severity of the DS phenotype. Our recent studies on DS fetal hearts and fibroblasts have suggested that one of the possible causes of mitochondrial dysfunction is the downregulation of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α or PPARGC1A)--a key modulator of mitochondrial function--and of several nuclear-encoded mitochondrial genes (NEMGs). Re-analysis of publicly available expression data related to manipulation of chromosome 21 (Hsa21) genes suggested the nuclear receptor interacting protein 1 (NRIP1 or RIP140) as a good candidate Hsa21 gene for NEMG downregulation. Indeed, NRIP1 is known to affect oxidative metabolism and mitochondrial biogenesis by negatively controlling mitochondrial pathways regulated by PGC-1α. To establish whether NRIP1 overexpression in DS downregulates both PGC-1α and NEMGs, thereby causing mitochondrial dysfunction, we used siRNAs to decrease NRIP1 expression in trisomic human fetal fibroblasts. Levels of PGC-1α and NEMGs were increased and mitochondrial function was restored, as shown by reactive oxygen species decrease, adenosine 5'-triphosp...Continue Reading


Sep 15, 2014·Biochemical and Biophysical Research Communications·Xiyuan LiuMinsun Chang
Mar 8, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Qing MuJingzhu Guo
Aug 25, 2018·Frontiers in Molecular Neuroscience·Macarena Gómez de SalazarXavier Altafaj
May 6, 2020·International Journal of Molecular Sciences·Nunzia MolloAntonella Izzo
Jul 19, 2019·Frontiers in Genetics·Nunzia MolloLucio Nitsch
Oct 24, 2017·International Journal of Genomics·Antonella IzzoLucio Nitsch
Feb 22, 2017·International Journal of Molecular Sciences·Anna KakehashiHideki Wanibuchi
Aug 24, 2018·Molecular Medicine·Antonella IzzoLucio Nitsch
Sep 24, 2020·International Journal of Molecular Sciences·Carmen Martínez-Cué, Noemí Rueda


Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·L S JouavilleR Rizzuto
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Sep 28, 2000·The Journal of Biological Chemistry·L N WeiM Farooqui
May 31, 2001·Methods in Cell Biology·A M PorcelliR Rizzuto
Apr 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sylvia N SchreiberAnastasia Kralli
Dec 21, 2004·Biochimica Et Biophysica Acta·Debra A O'LearySika Ristevski
Jun 28, 2005·Nucleic Acids Research·Bing ZhangJay Snoddy
Nov 16, 2005·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·G Stennis WatsonSuzanne Craft
Mar 24, 2006·Nature·Joseph R ArronGerald R Crabtree
Jul 4, 2006·Trends in Endocrinology and Metabolism : TEM·Mark ChristianMalcolm G Parker
Aug 8, 2006·Human Molecular Genetics·Ebrahim Abdul ShukkurKazuhiro Yamakawa
Mar 21, 2007·Medical Hypotheses·Wenpeng DongXiang Zhang
May 9, 2007·Bioscience Reports·Lucia PetrozziMichelangelo Mancuso
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sibylle JägerBruce M Spiegelman
Nov 2, 2007·The EMBO Journal·Evangelos KiskinisMalcolm G Parker
Jan 24, 2008·The Journal of Biological Chemistry·Miia M Rytinki, Jorma J Palvimo
Sep 12, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nektaria NicolakakisEdith Hamel
Dec 27, 2008·Biochemical and Biophysical Research Communications·Luis EscribanoDiana Frechilla
Jul 25, 2009·The Journal of Biological Chemistry·Miia M Rytinki, Jorma J Palvimo
Nov 20, 2009·Neurobiology of Aging·Tomohiko SatoToshihiko Iwamoto
Jun 10, 2010·American Journal of Physiology. Endocrinology and Metabolism·Asmaà FritahMalcolm G Parker
Jun 24, 2010·Genome Biology·Rossella De CegliGilda Cobellis
Oct 12, 2010·Biochimica Et Biophysica Acta·Richard C Scarpulla
Sep 24, 2011·Cell Communication and Signaling : CCS·Simone PatergnaniPaolo Pinton
Apr 25, 2012·Purinergic Signalling·Massimo BonoraPaolo Pinton
May 1, 2012·Progress in Brain Research·Rafael de la Torre, Mara Dierssen

Related Concepts

Chromosomes, Human, Pair 21
Biochemical Pathway
Specimen Type - Fibroblasts
RNA, Small Interfering
Cell Respiration
Down Syndrome
NRIP1 gene
Fetal Heart

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