Biology subjects

Gonzalez-Hernandez, M.

Publications and source records attributed to Gonzalez-Hernandez, M..

3 recordsLinked to original sources

bioRxiv2026

Membrane surface geometry is a determinant of mitochondrial electron transfer and cellular adaptation

Energy conversion in living organisms relies on biological membranes that facilitate electron transfer between oxidoreductases. In mitochondria, this process is mediated by the electron transport chain embedded in the inner mitochondrial membrane (IMM). Under various physiological and genetic conditions, mitochondrial matrix Na+ levels increase, reducing IMM fluidity through the formation of ternary coordination adducts between Na+ and phospholipids. These adducts impair ubiquinone (CoQ) transfer between respiratory complexes, thereby promoting mitochondrial reactive oxygen species (mtROS) production and activating the hypoxic adaptive pathway. Here, we show that modifying solely the ionic subatomic interaction with phospholipids is sufficient to prevent initiation of this pathway. Compound A (CA) outcompetes Na+ for phospholipid binding without impairing CoQ transfer, thereby preventing mtROS production and hypoxic adaptation. This divergence arises from the penta-coordinate complexes formed by CA with phospholipids, in contrast to the trigonal adducts formed by Na+. This structural distinction preserves IMM fluidity because CA:phospholipid assemblies adopt a less angular configuration. These findings establish membrane-surface geometry, modulated by ion:phospholipid interactions, as an unexpected determinant of membrane biology, mitochondrial energy conversion, redox signalling, and cellular adaptation, with profound implications for physiology and disease.

biochemistry↗

bioRxiv2022

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity. One sentence summaryA human monoclonal antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

microbiology↗

bioRxiv2018

Natural Secretory Immunoglobulins Enhance Norovirus Infection

Secretory immunoglobulins (SIg) are a first line of mucosal defense by the host. They are secreted into the gut lumen via the polymeric immunoglobulin receptor (pIgR) where they bind to antigen and are transported back across the FAE via M cells. Noroviruses are highly prevalent, enteric pathogens that cause significant morbidity, mortality and economic losses worldwide. Murine norovirus (MNV) exploits microfold (M) cells to cross the lymphoid follicle-associated epithelium (FAE) and infect the underlying population of immune cells. However, whether natural, innate SIg can protect against norovirus infection remains unknown. To investigate the role of natural SIg during murine norovirus pathogenesis, we used pIgR-deficient animals, which lack SIg in the intestinal lumen. Contrary to other enteric pathogens, acute MNV replication was significantly reduced in the gastrointestinal tract of pIgR-deficient animals compared to controls, despite increased numbers of dendritic cells, macrophages, and B cells in the Peyers patch, established MNV target cell types. Also, natural SIg did not alter MNV FAE binding or FAE crossing into the lymphoid follicle. Instead, further analysis revealed enhanced baseline levels of the antiviral molecules interferon gamma (IFN{gamma}) and inducible nitric oxide synthase (iNOS) in the small intestine of naive pIgR-deficient animals compared to controls. Removing the microbiota equalized IFN{gamma} and iNOS transcript levels as well as MNV viral loads in germ-free pIgR KO mice compared to germ-free controls. These data are consistent with a model whereby SIg sensing reduces pro-inflammatory, antiviral molecules, which facilitates intestinal homeostasis but thereby promotes MNV infection. In conclusion, these findings demonstrate that natural SIg are not protective during norovirus infection in mice and represent another example of indirect modulation of enteric virus pathogenesis by the microbiota.

microbiology↗