A5091534407- Autophagy in Disease and Therapy
- Spaceflight effects on biology
- Cell death mechanisms and regulation
- High Altitude and Hypoxia
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Human Health and Disease
- Biochemical effects in animals
- NF-κB Signaling Pathways
- Toxoplasma gondii Research Studies
- Melanoma and MAPK Pathways
- Erythropoietin and Anemia Treatment
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- MicroRNA in disease regulation
- Hemoglobin structure and function
- Viral Infections and Immunology Research
- RNA modifications and cancer
- Medical and Biological Ozone Research
- Immune Response and Inflammation
- Genetic Neurodegenerative Diseases
- Hippo pathway signaling and YAP/TAZ
Institute for Research in Biomedicine
2012-2024
Universitat de Barcelona
2012-2024
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2012-2024
Instituto de Salud Carlos III
2012-2024
Institute of Biomedical Problems
1992-2022
Centro de Investigación Biomédica en Red
2021
Faculty (United Kingdom)
2015
Russian Academy of Sciences
2005-2014
Central Clinical Hospital No 2 named Semashko
2013
Jožef Stefan Institute
2005-2011
In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a tether that interacts with an unknown partner on the endoplasmic reticulum (ER). this work, we identified MFN2 splice variant ERMIT2 ER tethering of MFN2. Splicing produced and ERMIN2, two ER-specific variants. ERMIN2 regulated morphology, whereas localized ER-mitochondria interface interacted mitochondrial mitofusins to mitochondria. This allowed...
A precise balance between protein degradation and synthesis is essential to preserve skeletal muscle mass. Here, we found that TP53INP2, a homolog of the Drosophila melanogaster DOR regulates autophagy in cellular models, has direct impact on mass vivo. Using different transgenic mouse demonstrated muscle-specific overexpression Tp53inp2 reduced mass, while deletion resulted hypertrophy. TP53INP2 activated basal sustained p62-independent autophagic ubiquitinated proteins. Animals with...
Abstract Apoptosis and senescence are two mutually exclusive cell fate programs that can be activated by stress. The factors instruct cells to enter into or apoptosis not fully understood, but both regulated the stress kinase p38α. Using an inducible system specifically activates this pathway, we show sustained p38α activation suffices trigger massive autophagosome formation enhance basal autophagic flux. This requires concurrent effect of increased mitochondrial reactive oxygen species...
Death receptor ligand TRAIL is a promising cancer therapy due to its ability selectively trigger extrinsic apoptosis in cells. However, TRAIL-based therapies humans have shown limitations, mainly inherent or acquired resistance of tumor To address this issue, current efforts are focussed on dissecting the intracellular signaling pathways involved TRAIL, identify strategies that sensitize cells TRAIL-induced cytotoxicity. In work, we describe oncogenic MEK5-ERK5 pathway as critical regulator...
The synthesis of a new small library quinoxaline-containing peptides is described. After cytotoxic evaluation in four human cancer cell lines, as well detailed biological studies, it was found that the most active compound, RZ2, promotes formation acidic compartments, where accumulates, blocking progression autophagy. Further disruption mitochondrial membrane potential and an increase ROS observed, causing cells to undergo apoptosis. Given its activity protease-resistant features, RZ2 could...
MFN1 (mitofusin 1) and MFN2 are key players in mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria juxtaposition, macroautophagy/autophagy. However, the mechanisms by which these proteins participate processes poorly understood. Here, we studied interactomes of two using CRISPR-Cas9 technology to insert an HA-tag at C terminus MFN2, thus generating HeLa cell lines that endogenously expressed MFN1-HA or MFN2-HA. HA-affinity isolation followed mass spectrometry identified potential...
The death receptor Fas/CD95 initiates apoptosis by engaging diverse cellular organelles including endosomes. link between Fas signaling and membrane traffic has remained unclear, in part because it may differ cell types. After a systematic investigation of all known pathways endocytosis, we have clarified that activation opens clathrin-independent portals mature T cells. These drive rapid internalization surface proteins such as CD59 depend upon actin-regulating Rho GTPases, especially...
DOR is a bi‐functional protein that regulates transcription and enhances starvation‐induced autophagy. While autophagy has been mostly described as stress–response mechanism, cells also need to maintain homeostasis in basal conditions. However, the mechanisms regulating still remain unknown. Our results show acts Indeed, already undergoes nucleo‐cytoplasmic shuttling conditions and, surprisingly, exits continuously nucleus traverses nucleolus. nucleolus integrity not essential for both...
A major feature of apoptotic cell death is gross structural changes, one which the loss cell–cell contacts. The caspases, executioners apoptosis, were shown to cleave several proteins involved in formation junctions. membrane-associated guanylate kinases (MAGUKs), are typically associated with junctions, have a role organization protein–protein complexes at plasma membranes and therefore potentially important caspase targets during apoptosis. We report here that MAGUKs cleaved and/or...
Cell-cell detachment is one of the hallmarks apoptosis. To date, several transmembrane and plaque proteins from tight adherent junctions have been characterised as caspase targets during Human discs large protein (hDLG)/SAP97 a member membrane-associated guanylate kinase (MAGUK) family proteins, localised at epithelial endothelial cells, that required for adherens junction assembly differentiation. Here, hDLG shown to be target UV irradiation staurosporine (STS)-induced apoptosis in HaCaT...
Abstract MAGI-1 is a membrane-associated guanylate kinase (MAGUK) protein present at adherent and tight junctions, where it acts as structural signaling scaffold. During apoptosis, cleaved by caspases Asp761 into N- C-terminal cleavage products, allowing further dismantling of the cell one key features apoptosis. Here, we investigated cellular distribution possible proapototic role caspase products. Full-length exhibited submembrane localization, while N-terminal product translocated to...