Biology subjects

Garrido, G.

Publications and source records attributed to Garrido, G..

3 recordsLinked to original sources

bioRxiv2026

Gαq-mediated contact release is required for efficient mitochondrial quality control

Lysosomes and mitochondria are highly dynamic organelles whose coordinated interactions are essential for cellular homeostasis, while their dysfunction contributes to numerous human diseases. Here, we identify the mitochondrial outer membrane protein Fis1 and the RabGAPs TBC1D15 and TBC1D17 as novel interacting partners of the heterotrimeric G protein -subunit Gq. Using mitochondrial proteomics, co-immunoprecipitation, proximity ligation assays, and in vitro binding studies with purified proteins, we demonstrate that Gq forms a complex with Fis1 and TBC1D15/TBC1D17 through a non-canonical interaction interface. Gq localizes to mitochondria-lysosome contact sites, where it regulates the dynamic balance between contact formation and dissociation. Loss of Gq resulted in enlarged and clustered lysosomes and increased the extent and duration of mitochondria-lysosome contacts. Live-cell imaging revealed prolonged organelle tethering in Gq-deficient cells, while proximity ligation and three-dimensional reconstruction analyses localized Gq and TBC1D15 to mitochondrial tips closely associated with lysosomes. This localization, together with increased mitochondrial fission and altered mitophagic turnover following Gq loss, links the regulation of contacts at mitochondrial tips to mitochondrial fragmentation and quality control. Re-expression of Gq, but not the non-canonical interaction-deficient mutant, restored normal lysosomal morphology, contact-site dynamics, mitochondrial fragmentation, and mitophagy. Together, these findings identify a Gq as a dynamic regulator of mitochondria-lysosome untethering and connect contact site turnover with mitochondria fragmentation and mitophagy. Our work uncovers a novel link between G protein signaling, organelle communication, and mitochondrial quality control.

cell biology↗

bioRxiv2025

Involvement of monoaminergic and nitrergic pathways in the behavioral effects and acute toxicity of Gomphrena perennis L. tincture in mice

Gomphrena perennis L. possesses a rich phenolic profile and has demonstrated cardiovascular and anti-inflammatory activities; however, its neuropharmacological properties re-main unexplored. The behavioral effects, underlying mechanisms, and acute toxicity of Gomphrena perennis tincture (GphT) were investigated in mice. GphT showed no signs of acute toxicity. Furthermore, it did not alter the number of cross lines in the open field test (OFT), but it induced anxiogenic responses in the elevated plus-maze test (EPM) and the novelty-suppressed feeding test (NSFT), which were reversed by L-NAME, a non-selective nitric oxide synthases inhibitor. GphT also reduced immobility time in the forced swimming test (FST) and the tail suspension test (TST). This antidepressant-like effect was prevented by haloperidol (D1/D2 antagonist), ketanserin (5-HT2A/2C antagonist), L-NAME, and sildenafil (PDE5 inhibitor), while propranolol ({beta}-blocker), prazosin (1-an-tagonist), yohimbine (2-antagonist), and ondansetron (5-HT3-antagonist) did not modify it. Therefore, GphT produced anxiogenic and antidepressant-like effects without im-pairing locomotion. These effects involve dopaminergic and serotonergic pathways and depend on nitric oxide-mediated signaling, suggesting that GphT exerts a modulatory influence on interconnected neurochemical systems.

pharmacology and toxicology↗

bioRxiv2018

Consensus interpretation of the Met34Thr and Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel

PURPOSEPathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants.\n\nMETHODSThe ClinGen Hearing Loss Expert Panel (HL-EP) collected published data and shared unpublished information from participating laboratories regarding the two variants. Functional, computational, allelic, and segregation data were also obtained.\n\nRESULTSThe panel reviewed the synthesized information, and classified the Met34Thr and Val37Ile variants according to professional variant interpretation guidelines. We found that Met34Thr and Val37Ile are significantly overrepresented in hearing loss patients, compared to the general population. Met34Thr or Val37Ile homozygotes or compound heterozygotes typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for those two variants.\n\nCONCLUSIONResolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification rules, review evidence, and reach a consensus. The ClinGen HL-EP concluded that Met34Thr and Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and age-dependent penetrance.

genetics↗