Biology subjects

Romero-Sanz, S.

Publications and source records attributed to Romero-Sanz, S..

3 recordsLinked to original sources

bioRxiv2026

High-throughput screen identifies a potent MCU activator boosting cardiac contractile bioenergetics

Mitochondrial Ca2+ uptake through the mitochondrial calcium uniporter complex (MCUc) couples intracellular Ca2+ signaling to energy metabolism and cellular function. Despite its physiological importance, potent and selective pharmacological activators of the MCU complex remain scarce, and existing compounds show modest specificity. Here, we screened 1,280 bioactive compounds and identified CGP7930 as a potent activator of mitochondrial Ca2+ uptake. Mechanistically, the compound required MICU1, but not MICU2, to exert its effects. Molecular docking, non-covalent interaction analysis, and site-directed mutagenesis identified Gln304 and Val307 in MICU1 as critical determinants of compound activity. In addition to directly stimulating MCU activity, CGP7930 increased mitochondria-endoplasmic reticulum contact sites, suggesting an additional mechanism to facilitate inter-organellar Ca2+ transfer. CGP7930 promoted Ca2+-dependent activation of mitochondrial energy metabolism in cardiomyocytes and boosted the contractile performance of the mice hearts. This effect was MCU-dependent, as hearts from MCU KO mice failed to increase the ventricular contraction force upon CGP7930 perfusion. Molecular docking, non-covalent interaction analysis, and site-directed mutagenesis identified Gln304 and Val307 in MICU1 as critical determinants of compound activity.

biochemistry↗

bioRxiv2025

Nutrient-Responsive Formation of Mitochondrial-Derived Structures in Caenorhabditis elegans

Mitochondrial morphology is dynamically regulated through remodeling processes essential for maintaining mitochondrial function and ensuring cellular and metabolic homeostasis. While classical models of mitochondrial dynamics center on cycles of fragmentation and elongation, emerging evidence highlights additional membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and mitochondrial-derived compartments (MDCs). These mitochondrial-derived structures, however, have been predominantly characterized in cultured cells and unicellular organisms, leaving their relevance in multicellular systems largely unexplored. Here, we identify a previously uncharacterized class of mitochondrial-derived structures in Caenorhabditis elegans muscle cells that are induced in response to intermittent fasting. We show that these structures appear specifically during the refeeding phase-- coinciding with mitochondrial elongation --and are absent during fasting. Consistent with MDCs, the structures, approximately 1 {micro}m in size, are enriched in outer mitochondrial membrane markers such as TOMM-20aa1-49 and TOMM-70, but notably lack components of the inner mitochondrial membrane. Their formation requires the microtubule-associated MIRO-1/2 proteins, and their size is modulated by the mitochondrial dynamics machinery. Together, our findings reveal a nutritionally regulated mitochondrial remodeling event in C. elegans muscle that may play a role in mitochondrial quality control and adaptation to metabolic cues.

cell biology↗

bioRxiv2024

Novel Imaging Tools to Study Mitochondrial Dynamics in Caenorhabditis elegans

Mitochondria exhibit a close interplay between their structure and function. Understanding this intricate relationship requires advanced imaging techniques that can capture the dynamic nature of mitochondria and their impact on cellular processes. However, much of the work on mitochondrial dynamics has been done in single celled organisms or in vitro cell culture. Here, we introduce novel genetic tools for live imaging of mitochondrial networks in the nematode Caenorhabditis elegans, addressing a pressing need for advanced techniques in studying organelle dynamics within live intact multicellular organisms. Through a comprehensive analysis, we directly compare our tools with existing methods, demonstrating their advantages for visualizing mitochondrial morphology and contrasting their impact on organismal physiology. We reveal limitations of conventional techniques, while showcasing the utility and versatility of our approaches, including endogenous CRISPR tags and ectopic labeling. By providing a guide for selecting the most suitable tools based on experimental goals, our work advances mitochondrial research in C. elegans and enhances the strategic integration of diverse imaging modalities for a holistic understanding of organelle dynamics in living organisms.

cell biology↗