Biology subjects

Guerra-Castellano, A.

Publications and source records attributed to Guerra-Castellano, A..

3 recordsLinked to original sources

bioRxiv2026

Human NLRP1 and NLRP3 interact driving inflammation in inflammosomopathies and inflammatory diseases

Inflammasomes are multiprotein complexes that form and activate after exposure to pathogenic microbes and host danger signals that trigger an inflammatory response. Although NLRP1 and NLRP3 inflammasomes share structural similarities and can be activated by similar stimuli, no evidence of heterotypic inflammasome assemblies has been reported. Here, we identify a unique interaction between NLRP1 and NLRP3 in human cells, forming a hybrid inflammasome, to drive inflammation. NLRP1 is essential for this hydrid inflammasome activation and NLRP3-mediated Caspase-1 activation and release of IL-1{beta} and IL-18. The presence of the heterocomplex inflammasome was confirmed in blood samples from patients after kidney transplantation and is associated with inflammatory responses driven by NLRP3 and MEFV mutations that cause inflammasomopathies. Our findings reveal an unexpected level of intricacy in inflammasome composition, pinpointing hybrid targets that may pave the way for innovative pharmacological treatments for inflammatory disorders. Significance StatementPrevious findings showed interactions between NLRP3 and NLRC4 or NLRP3 and NLRP11 showing that would be possible the interaction of the inflammasomes as supercomplexes and not working alone. Now, we show a new inflammasome heterocomplex inflammasome between NLRP1 and NLRP3 which is associated to the inflammatory profile in autoimmune diseases patietns and transplanted patients. These findings could open a new research topic for the design of dual inflammasomes inhibitors.

immunology↗

bioRxiv2024

Unveiling the role of yeast cytochrome c isoforms in the assembly of mitochondrial supercomplexes and the control of respiratory chain rate

Mitochondria play crucial roles as both the powerhouse and signaling center of cells, balancing cell survival and death to maintain homeostasis. Disruption of this balance can lead to various diseases. Therefore, exploring the components involved in mitochondrial metabolism presents a significant challenge. In this context, respiratory supercomplexes are evolutionarily conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. These supercomplexes dynamically respond to metabolic demands, enhancing the electron transfer rate and reducing the production of reactive oxygen species. Recent research has identified cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in the formation of these supercomplexes. This study focuses on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the yeast Saccharomyces cerevisiae as a model system for mitochondrial metabolism. Our findings indicate that the viability of Saccharomyces cerevisiae relies on the presence of cytochrome c, with both isoforms playing a role in the assembly of respiratory supercomplexes. Notably, isoform-2 of cytochrome c enhances electron transfer efficiency, resulting in reduced ROS production.

biophysics↗

bioRxiv2024

NMR based metabolomic workflow to unravel the molecular mechanisms involved in strawberry vernalization

Metabolomics is the discipline that aims to determine the whole metabolic profile of a complex mixture. These studies are useful to capture the physiological status of an organism at a given moment. Even though the main technique used in metabolomics is Mass Spectrometry coupled to chromatography, in recent years, interest in Nuclear Magnetic Resonance (NMR) is increasing because of some benefits of NMR, i.e., it is a non-invasive, highly reproducible, and inherently quantitative technique. However, difficulties in data analysis comprise one of the main reasons that hinder the standardization of NMR for metabolomic analysis in research. In this work, we applied an automated workflow for NMR-based metabolomic analysis for the study of vernalization in strawberry. Vernalization is a key process in obtaining a successful strawberry crop, however, the molecular mechanisms behind it remain still unknown. We expect this work to improve the knowledge of crop metabolism --specifically the vernalization process-- while promoting the use of NMR in conjunction with computational tools for agriculture studies.

biochemistry↗