Condensados Biomoleculares: Organizadores de la Vida

Life never fails to surprise us. Today, it does so with membrane-less organelles known as biomolecular condensates. These structures arise from a phenomenon of biomolecular self-organization capable of generating localized microenvironments with defined functions within the cell. In recent years, the significance of condensates in various aspects of cellular biology has been  unveiled, including the regulation  of gene expression, protein synthesis, cellular signaling control, cytoskeletal protein polymerization, and the formation of aggregates associated with neurodegenerative diseases, among many others yet to be discovered. These findings are revolutionizing our current understanding of cellular processes and providing new insights into cell process regulation. Condensates unveil previously unknown cellular mechanisms, more stochastic, that are shifting away from the dominance of genetic mechanisms in favor of cellular self-organization processes. The advancement in comprehending biomolecular condensates paves the way for exciting avenues of research in cellular and molecular biology, enabling the reinterpretation of processes that relate the genotype to the phenotype. Offering, in this way, the potential to better understand diseases and develop more effective therapeutic approaches in the future.La vida nunca deja de sorprendernos. Hoy lo hace con unos orgánulos libres de membrana conocidos como condensados biomoleculares. Éstos, son el resultado de un fenómeno de autoorganización de biomoléculas capaz de crear auténticos microentornos con funciones definidas en el interior de la célula. En los últimos años, se ha descubierto que los condensados desempeñan un papel relevante en diversos aspectos de la biología celular, como la regulación de la expresión génica, la síntesis de proteínas, el control de la señalización celular, la polimerización de proteínas del citoesqueleto o la formación de agregados asociados a enfermedades neurodegenerativas, entre muchas otras aún por descubrir. Estos hallazgos están desafiando nuestra comprensión actual de los procesos celulares y ofrecen nuevas maneras de entender el funcionamiento interno de las células. Los condensados muestran mecanismos celulares previamente desconocidos, mucho más estocásticos y que diluyen la preponderancia del mecanicismo genético en favor de los procesos de autoorganización celular. El avance en la comprensión de los condensados biomoleculares abre emocionantes vías de investigación en biología celular y molecular y permiten la reinterpretación de los procesos que relacionan el genotipo y el fenotipo, ofreciendo así la posibilidad de comprender mejor las enfermedades y desarrollar enfoques terapéuticos más efectivos en el futuro

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality