Biology subjects

Fu, C.-Y.

Publications and source records attributed to Fu, C.-Y..

3 recordsLinked to original sources

bioRxiv2025

Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis

Regulation of intracellular ascorbic acid (AA) levels is critical for connective tissue development and maintenance, but the underlying mechanisms remain unclear. In this study, we uncover a novel regulatory role of glucose transporter 10 (GLUT10) in AA homeostasis through a noncanonical trafficking pathway from the endomembrane system to mitochondria, traditionally considered as separate entities. We demonstrate that GLUT10 transit from ER to mitochondria through the plasma membrane (PM) and endosomes increases under stress conditions. This PM localization enhances the transport of dehydroascorbic acid (DHA), the oxidized form of AA, thereby maintaining intracellular AA levels. Disruption of this trafficking impairs AA homeostasis. Our findings reveal a previously unrecognized localization of GLUT10 at the PM and endosomes, highlighting a novel communication between endomembrane system and mitochondria for proetin redistribution, which is essential for maintaining intracellular AA homeostasis and facilitating environmental adaptation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/632083v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@17ac1d1org.highwire.dtl.DTLVardef@4aa2f3org.highwire.dtl.DTLVardef@101849org.highwire.dtl.DTLVardef@aa9c26_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Sulfite oxidase deficiency causes persulfidation loss and H2S release

Sulfite oxidase (SOX) deficiency is a rare inborn error of cysteine metabolism resulting in severe neurological damage. In patients, sulfite accumulates to toxic levels causing a raise in downstream products S-sulfocysteine (SSC), mediating excitotoxicity, and thiosulfate, a catabolic intermediate/product of H2S metabolism. Here, we report a full-body knock-out mouse model for SOX deficiency (SOXD) with a severely impaired phenotype. Amongst the urinary biomarkers, thiosulfate showed a 45-fold accumulation in SOXD mice representing the major excreted S-metabolite. Consistently, we found increased plasma H2S, which was derived from sulfite-induced release from persulfides as demonstrated in vitro and in vivo. Mass spectrometric analysis of total protein persulfidome identified a major loss of persulfidation in 20% of the proteome affecting enzymes in amino acids and fatty acid metabolism. Urinary amino acid profiles indicate metabolic rewiring suggesting partial reversal of the TCA cycle thus identifying a novel contribution of H2S metabolism and persulfidation in SOXD.

biochemistry↗

bioRxiv2021

A systematic analysis of diet-induced nephroprotection reveals overlapping and conserved changes in cysteine catabolism

Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection as well as overlapping metabolic consequences has not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a potential common mechanism of organ protection. Importantly, these metabolic changes can be recapitulated in patients preconditioned by a diet limiting sulfur-containing amino acids indicating conserved diet-induced mechanisms of stress-resistance that may ultimately lead to clinical application.

biochemistry↗