135 research outputs found
Editorial: Oncogenic RAS-Dependent Reprogramming of Cellular Plasticity.
No full textNo abstract availlable
Analysis of the modulation of the MCU complex expression and activity in stomach and colorectal cancers
No full textMitochondrial Ca2+ transport is a highly conserved phenomenon that is linked to a diverse set of cellular processes, including programmed cell death and inflammation. Given the lack of cell-permeant uniporter inhibitors and the previously unknown molecular identity of the uniporter, the functional studies to date have been largely correlative. The innovative aspect of the current project consists in carrying out a set of targeted genetic and biochemical studies that will enable a detailed molecular understanding of mitochondrial Ca2+ uptake and the mechanisms that govern its regulation. Moreover it offers initial clues to the relevance of these pathways in human stomach and colorectal cancers and highlights the importance of mitochondrial Ca2+ regulation in tumor progression
Exploiting “oncogene addiction” and “premature senescence” to design novel therapeutic strategies for the treatment of cancer
No full textL’obiettivo principale del presente progetto è rappresentato dall'indagine del ruolo del segnale Ca2+ nei fenomeni di progressione e mantenimento tumorale promossi dall'oncogene RAS. Aumentare le nostre conoscenze circa il coinvolgimento del mitocondrio e della sua capacità d'interpretare segnali Ca2+ nel sostenere il fenotipo neoplastico. Far luce sui processi di OIS innescati dall'oncogene RAS, e capire come questi sono evasi nelle cellule tumorali. Lo scopo ultimo è d'identificare nuove vie di segnalazione intracellulare che potrebbero poi rappresentare nuovi bersagli terapeutici
A combination of miR501-5p and mTOR as molecular markers for the prognosis of renal carcinomas
No full text• Analisi dell’espressione del miR501-5p in campioni di tessuto di carcinoma renale e linee cellulari derivate da tumore renale.
• Caratterizzazione della funzione del miR501-5p nel carcinoma renale e identificazione di vie del segnale associate con la proliferazione cellulare, l’apoptosi, l’autofagia e modulate dal miR501-5p.
• Analisi del ruolo di mTOR e TP53 nel carcinoma renale in relazione con l’espressione del miR501-5p
Mitochondrial quality control machinery a role in the P. aeruginosa-triggered inflammatory response in Cystic Fibrosis
No full textPrincipal investigator, project FFC20/2015: The overall goal of this project is to broaden our knowledge
on role in vitro of mitochondrial quality control machinery to decode the pro-inflammatory signals
generated during P. aeruginosa infection in CF. Our attention is addressed to investigate about the
balance between xenophagy, mitophagy and UPRmt in P. aeruginosa-dependent inflammation response
and identify which mechanism fail during CF pathogenesis
Differential recruitment of PKC isoforms in HeLa cells during redox stress.
No full textThe protein kinase C (PKC) family is a major transducer of several intracellular pathways. In confirmation of this important role, PKCs exhibit high molecular heterogeneity, because they occur in at least 10 different isoforms differing in biochemical properties and sensitivity to activators. In this report we focused on the ability of different redox agents to induce modification of intracellular distribution of specific PKC isoforms in HeLa cells. To this end we utilized a panel of green fluorescent protein (GFP) chimeras and a high-speed digital imaging system. We observed a remarkable complexity of PKC signalling patterns occurring during redox stress with marked differences among PKC isoforms also belonging to the same subgroup. Moreover our results suggest that modifications of the intracellular redox state can modulate the responsiveness of specific PKC isoforms and, in turn, change the sensitivity of the different isoforms to cell stimulation
A shape to fit the need: how cell rearrange their organelle composition and architecture during development and stress (PRIN 2017, codice 2017XA5J5N)
No full textOur proposal investigates how cells reshape their organelles during development towards a secretory specialization, focusing on the mitochondria-endoplasmic reticulum (ER) contacts. It starts from the assumption that a higher ATP demand imposed by increased ER protein folding and degradation could be satisfied by formation of functional contacts with mitochondria. Revisiting mitochondrial-associated membranes (MAM) biogenesis under dynamic conditions will allow identifying molecules and patterns induced to satisfy the increased energetic demand. To this end, we will deploy state of the art quantitative proteomics and imaging technologies to analyze cellular systems induced to synthesize abundant secretory proteins with different fates, recently developed and characterized in our labs (Bakunts et al., 2017). Do MAM increase/change in parallel to the expansion of the secretory pathway? Does an increased ATP demand in the ER induce more/tighter MAM? Do different cargoes impact the outcome, and if so how? Does the unfolded protein response drive MAM reshaping, and if so via which branch(es)? Our experiments will shed light on fundamental functions of eukaryotic cells with relevance for various diseases that originate from altered ER and mitochondrial functions
The versatility of mitochondrial calcium signals: From stimulation of cell metabolism to induction of cell death
No full textBoth the contribution of mitochondria to intracellular calcium (Ca2+) signalling and the role of mitochondrial Ca2+ uptake in shaping the cytoplasmic response and controlling mitochondrial function are areas of intense investigation. These studies rely on the appropriate use of emerging techniques coupled with judicious data interpretation to a large extent. The development of targeted probes based on the molecular engineering of luminescent proteins has allowed the specific measurement of Ca2+ concentration ([Ca2+]) and adenosine trisphosphate concentration ([ATP]) in intracellular organelles or cytoplasmic subdomains. This approach has given novel information on different aspects of mitochondrial homeostasis. (c) 2008 Elsevier B.V. All rights reserved
H-Ras-driven tumoral maintenance is sustained through caveolin-1-dependent alterations in calcium signaling
No full textA growing body of research has highlighted the complex range of tumoral traits acquired during H-Ras-driven transformation and maintenance, which include proliferative signaling, growth suppressor evasion and resistance to cell death. Clear molecular information about these processes is not yet available, but recent evidence has provided solid support for the importance of mitochondria. Here, we show that the induction of oncogenic H-Ras leads to changes in intracellular calcium (Ca2+), evaluate the temporal relationship between oncogene expression and mitochondrial physiology, and demonstrate that Ca2+ homeostasis is altered by caveolin-1, a protein that has a key role in tumor maintenance. Our results indicate that tumor-suppressor caveolin-1 is a core component of the Ca2+-dependent apoptotic pathway and participates in the regulation of critical mitochondrial functions during tumor development. The compromised caveolin-1/Ca2+ axis contributes to failure in both mitochondrial metabolism and apoptosis, thereby sustaining the neoplastic phenotype. These results illustrate a direct link between Ca2+ regulation and mitochondrial biology in cance
Mitochondrial Stress Responses and "Mito-Inflammation" in Cystic Fibrosis
No full textCystic fibrosis (CF) is a genetic disease associated to mutations in the cystic fibrosis transmembrane conductance regulator gene, which results in the alteration of biological fluid and electrolyte homeostasis. The characteristic pathological manifestation is represented by exaggerated proinflammatory response in lung of CF patients, driven by recurrent infections and worsen by hypersecretion of proinflammatory mediators and progressive tissue destruction. Treating inflammation remains a priority in CF. However, current anti-inflammatory treatments, including non-steroidal agents, are poorly effective and present dramatic side effects in CF patients. Different studies suggest an intimate relationship between mitochondria and CF lung disease, supporting the hypothesis that a decline in mitochondrial function endorses the development of the hyperinflammatory phenotype observed in CF lung. This allowed the implementation of a new concept: the "mito-inflammation," a compartmentalization of inflammatory process, related to the role of mitochondria in engage and sustain the inflammatory responses, resulting a druggable target to counteract the amplification of inflammatory signals in CF. Here, we will offer an overview of the contribution of mitochondria in the pathogenesis of CF lung disease, delving into mitochondrial quality control responses, which concur significantly to exacerbation of CF lung inflammatory responses. Finally, we will discuss the new therapeutic avenues that aim to target the mito-inflammation, an alternative therapeutic advantage for mitochondrial quality control that improves CF patient's inflammatory state
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