Abstract
Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis. Understanding how loss of LAMP-2 expression leads to cardiomyocyte dysfunction and heart failure has important implications for the treatment of Danon disease as well as a variety of other cardiac disorders associated with impaired autophagy. Elucidate the pathophysiology of cardiac dysfunction in Danon disease. We created hiPSCs from two patients with Danon disease and differentiated those cells into hiPSC-CMs using well-established protocols. Danon hiPSC-CMs demonstrated an accumulation of damaged mitochondria, disrupted mitophagic flux, depressed mitochondrial respiratory capacity, and abnormal gene expression of key mitochondrial pathways. Restoring the expression of LAMP-2B, the most abundant LAMP-2 isoform in the heart, rescued mi...Continue Reading
Citations
Apr 17, 2018·Human Molecular Genetics·Cui ZhangJinfu Wang
Dec 14, 2017·Essays in Biochemistry·Elena SeranovaSovan Sarkar
Aug 7, 2018·Autophagy·Alexa ParousisDavid A Hood
Dec 24, 2018·Cells·Jin LiBianca J J M Brundel
Mar 1, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Juliane C CamposJulio C B Ferreira
Aug 6, 2020·Journal of Clinical Medicine·Giorgia Del FaveroMatthew R G Taylor
Jun 3, 2018·Cells·Connor N BroylesMatthew J Daniels
Dec 18, 2019·Cells·Jin LiMarit Wiersma
May 7, 2020·Frontiers in Cell and Developmental Biology·Daniela Bakula, Morten Scheibye-Knudsen
Mar 20, 2020·Science Translational Medicine·Ana Maria MansoEric D Adler
Sep 7, 2019·International Journal of Molecular Sciences·Andreas BrodehlHendrik Milting
Dec 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Congwu ChiKunhua Song
Oct 17, 2018·Pflügers Archiv : European journal of physiology·Thomas Eschenhagen, Lucie Carrier
Dec 18, 2019·Journal of Clinical Medicine·Claudia SacchettoMartina Calore
Nov 28, 2020·Stem Cell Reviews and Reports·Mina KolahdouzmohammadiSara Pahlavan
May 26, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sarbari SahaSujit K Bhutia
Dec 4, 2019·Molecular Genetics and Metabolism·Benjamin L FarahDwight D Koeberl
Nov 6, 2020·Circulation. Genomic and Precision Medicine·Dor LotanUNKNOWN Cooperating Investigators‡
Mar 7, 2021·Journal of Clinical Medicine·Teresa PasquaTommaso Angelone
Jun 23, 2019·Journal of Molecular and Cellular Cardiology·Alexey V DvornikovXiaolei Xu
Nov 28, 2017·Journal of Molecular and Cellular Cardiology·Shohei YoshidaKenshi Hayashi
May 2, 2021·Molecular Aspects of Medicine·Xin WenDaniel J Klionsky
May 6, 2021·Cells·Matthew Triolo, David A Hood
Aug 8, 2021·International Journal of Molecular Sciences·Jennifer ZhangHung-Fat Tse
Aug 17, 2021·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Yasunori SuematsuShin-Ichiro Miura
Aug 31, 2021·Journal of the American Heart Association·Ronny AlcalaiChristine E Seidman