<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">León, Marian</style></author><author><style face="normal" font="default" size="100%">Prieto, Javier</style></author><author><style face="normal" font="default" size="100%">Molina-Navarro, María Micaela</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Barneo-Muñoz, Manuela</style></author><author><style face="normal" font="default" size="100%">Ponsoda, Xavier</style></author><author><style face="normal" font="default" size="100%">Sáez, Rosana</style></author><author><style face="normal" font="default" size="100%">Palau, Francesc</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Izpisua Belmonte, Juan Carlos</style></author><author><style face="normal" font="default" size="100%">Torres, Josema</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Rapid degeneration of iPSC-derived motor neurons lacking Gdap1 engages a mitochondrial-sustained innate immune response.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Death Discov</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell Death Discov</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2023 Jul 01</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">217</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Charcot-Marie-Tooth disease is a chronic hereditary motor and sensory polyneuropathy targeting Schwann cells and/or motor neurons. Its multifactorial and polygenic origin portrays a complex clinical phenotype of the disease with a wide range of genetic inheritance patterns. The disease-associated gene GDAP1 encodes for a mitochondrial outer membrane protein. Mouse and insect models with mutations in Gdap1 have reproduced several traits of the human disease. However, the precise function in the cell types affected by the disease remains unknown. Here, we use induced-pluripotent stem cells derived from a Gdap1 knockout mouse model to better understand the molecular and cellular phenotypes of the disease caused by the loss-of-function of this gene. Gdap1-null motor neurons display a fragile cell phenotype prone to early degeneration showing (1) altered mitochondrial morphology, with an increase in the fragmentation of these organelles, (2) activation of autophagy and mitophagy, (3) abnormal metabolism, characterized by a downregulation of Hexokinase 2 and ATP5b proteins, (4) increased reactive oxygen species and elevated mitochondrial membrane potential, and (5) increased innate immune response and p38 MAP kinase activation. Our data reveals the existence of an underlying Redox-inflammatory axis fueled by altered mitochondrial metabolism in the absence of Gdap1. As this biochemical axis encompasses a wide variety of druggable targets, our results may have implications for developing therapies using combinatorial pharmacological approaches and improving therefore human welfare. A Redox-immune axis underlying motor neuron degeneration caused by the absence of Gdap1. Our results show that Gdap1 motor neurons have a fragile cellular phenotype that is prone to degeneration. Gdap1 iPSCs differentiated into motor neurons showed an altered metabolic state: decreased glycolysis and increased OXPHOS. These alterations may lead to hyperpolarization of mitochondria and increased ROS levels. Excessive amounts of ROS might be the cause of increased mitophagy, p38 activation and inflammation as a cellular response to oxidative stress. The p38 MAPK pathway and the immune response may, in turn, have feedback mechanisms, leading to the induction of apoptosis and senescence, respectively. CAC, citric acid cycle; ETC, electronic transport chain; Glc, glucose; Lac, lactate; Pyr, pyruvate.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Prieto, Javier</style></author><author><style face="normal" font="default" size="100%">León, Marian</style></author><author><style face="normal" font="default" size="100%">Ponsoda, Xavier</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Bort, Roque</style></author><author><style face="normal" font="default" size="100%">Serna, Eva</style></author><author><style face="normal" font="default" size="100%">Barneo-Muñoz, Manuela</style></author><author><style face="normal" font="default" size="100%">Palau, Francesc</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">López-García, Carlos</style></author><author><style face="normal" font="default" size="100%">Torres, Josema</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Dysfunctional mitochondrial fission impairs cell reprogramming.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Cycle</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell Cycle</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Cycle Checkpoints</style></keyword><keyword><style  face="normal" font="default" size="100%">Cellular Reprogramming</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Damage</style></keyword><keyword><style  face="normal" font="default" size="100%">G2 Phase</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Knockdown Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondrial Dynamics</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Nerve Tissue Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Pluripotent Stem Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">3240-3250</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered a G2/M growth arrest in Gdap1-null cells undergoing reprogramming. High-Content analysis showed that this growth arrest was DNA damage-independent. We propose that lack of efficient mitochondrial fission impairs cell reprogramming by interfering with cell cycle progression in a DNA damage-independent manner.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">23</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/27753531?dopt=Abstract</style></custom1></record></records></xml>