Biology subjects

Goeminne, G.

Publications and source records attributed to Goeminne, G..

5 recordsLinked to original sources

bioRxiv2026

Spatially-restricted metabolic delivery of auxin for selective adventitious root induction

Auxin impacts on nearly every aspect of plant growth and development. Its exogenous application therefore results in pleiotropic growth responses. Exploiting this activity for plant propagation requires avoiding or minimizing such off-target effects and is generally achieved as a trade-off between toxicity and organogenetic efficacity. We recently identified the compound HYSPARIN (HYS) with potent, and uniquely selective adventitious root inductive activity. Unlike other root-inducing compounds, HYS preferentially activates auxin responses in the shoot via an unknown mechanism. Here, we show that HYS acts as a shoot-specific proauxin. Rather than acting through auxin homeostasis, we found that HYS is hydrolysed in planta independently of ILR1/ILL amidohydrolases to release the synthetic auxin MCPA. Structure-activity relationship analysis confirmed a strong dependence on its MCPA moiety for activating auxin responses, and identified its promoiety as a determinant of shoot-specificity and activity. Selective application of MCPA also potently induces AR is consistent with a model in which HYS metabolism produces a spatially restricted, AR inductive auxin signal. The activation mechanism of HYS thus provides a conceptual framework for tissue-specific metabolic delivery of auxin and may enable the programmable delivery of other xenobiotics in plants.

plant biology↗

bioRxiv2023

Integrating multiple omics levels using the human protein complexome as a framework, a multi-omics study of inborn errors of metabolism

Proteins organize into functional assemblies that drive diverse biological activities. Leveraging a comprehensive dataset of manually curated annotations for the human protein complexome, we investigated biological perturbations at the protein complex level. Using proteomics and transcriptomics data from fibroblasts of patients with inborn errors of metabolism (IEM) and control samples, we globally mapped information onto complex subunits to discern affected processes. Across the patient cohort (consisting of organic acidaemias, fatty acid oxidation defects and mitochondrial respiratory chain defect IEMs), mitochondrial oxidative phosphorylation emerged as the most perturbed pathway, identified through proteomics datasets. Simultaneously, metabolomics highlighted significant regulation of phospholipids in patients with Fatty Acid and Mitochondrial IEM. Moreover, proteomics analysis also revealed the dysregulation of protein complexes involved in histone (de)acetylation, a finding validated through Western Blot analysis measuring histone acetylation levels. This introduces a novel epigenetic dimension to IEM and metabolic research, suggesting avenues for further exploration. Our study demonstrates a multiomics data integration concept that maps proteomics and transcriptomics data onto model organism complexomes. This integrative approach can be extended to metabolomics and lipidomics, associating information with complexes having metabolic functions, such as enzymatic complexes. This global strategy for identifying disease-relevant perturbations offers a systems-wide perspective on molecular-level physiological and pathological changes. Such insights are crucial for devising clinical intervention strategies and prioritizing druggable pathways and complexes. The presented methodology provides a foundation for future investigations, emphasizing the importance of integrating multiomics data to comprehensively understand cellular machinery alterations and facilitate targeted therapeutic approaches.

biochemistry↗

bioRxiv2023

The selective estrogen receptor modulator clomiphene inhibits sterol biosynthesis in Arabidopsis thaliana

Sterols are produced via complex, multistep biosynthetic pathways involving similar enzymatic conversions in plants, animals and fungi, yielding a variety of sterol metabolites with slightly different chemical properties to exert diverse and specific functions. The role of plant sterols has been studied in the context of cell biological processes, signaling and overall plant development, mainly based on mutants. Due to their essential nature, genetic interference with their function causes pleiotropic developmental defects. An important alternative is to use a pharmacological approach. However, the current toolset for manipulating sterol biosynthesis in plants remains limited. Here, we probed a collection of inhibitors of mammalian cholesterol biosynthesis to identify new inhibitors of plant sterol biosynthesis. We provide evidence that imidazole-type fungicides, bifonazole, clotrimazole and econazole inhibit the obtusifoliol 14-demethylase CYP51, that is highly conserved among eukaryotes. Surprisingly, we found that the selective estrogen receptor modulator, clomiphene, inhibits sterol biosynthesis, in part by inhibiting the plant-specific cyclopropyl-cycloisomerase CPI1. These results demonstrate that rescreening of the animal sterol biosynthesis pharmacology is an easy approach for identifying novel inhibitors of plant sterol biosynthesis. Such molecules can be used as entry points for the development of plant-specific inhibitors of sterol biosynthesis that can be used in agriculture.

plant biology↗

bioRxiv2020

Loss of a subunit of vacuolar ATPase identifies unexpected biological signatures of reduced organelle acidification in vivo

The inability to maintain a strictly regulated endo(lyso)somal acidic pH through the proton-pumping action of the vacuolar-ATPases has been associated with various human diseases including heritable connective tissue disorders, neurodegenerative diseases and cancer. Multiple studies have investigated the pleiotropic effects of reduced acidification in vitro, but the mechanisms elicited by impaired endo(lyso)somal acidification in vivo remain poorly understood. Here, we show that loss of atp6v1e1b in zebrafish leads to early mortality, associated with craniofacial dysmorphisms, vascular anomalies, cardiac dysfunction, hypotonia and epidermal structural defects, reminiscent of the phenotypic manifestations in cutis laxa patients carrying a defect in the ATP6V1E1 gene. Mechanistically, we found that in vivo genetic depletion of atp6v1e1b leads to N-glycosylation defects and reduced maturation of endosomal and lysosomal vesicles, but retains the hypoxia-mediated response. In order to gain further insights into the processes affected by aberrant organelle acidification, we performed an untargeted analysis of the transcriptome and metabolome in early atp6v1e1b-deficient larvae. We report multiple affected pathways including but not limited to oxidative phosphorylation, sphingolipid and fatty acid metabolism with profound defects in mitochondrial respiration. Taken together, our results identify new complex biological effects of reduced organelle acidification in vivo, which likely contribute to the multisystemic manifestations observed in disorders caused by v-ATPase deficiency.

molecular biology↗

bioRxiv2019

Compensatory guaiacyl lignin biosynthesis at the expense of syringyl lignin in 4CL1-knockout poplar

The lignin biosynthetic pathway is highly conserved in angiosperms, yet pathway manipulations give rise to a variety of taxon-specific outcomes. Knockout of lignin-associated 4-coumarate:CoA ligases (4CLs) in herbaceous species mainly reduces guaiacyl (G) lignin and enhances cell wall saccharification. Here we show that CRISPR-knockout of 4CL1 in Populus tremula x alba preferentially reduced syringyl (S) lignin, with negligible effects on biomass recalcitrance. Concordant with reduced S-lignin was downregulation of ferulate 5-hydroxylases (F5Hs). Lignification was largely sustained by 4CL5, a low-affinity paralog of 4CL1 typically with only minor xylem expression or activity. Levels of caffeate, the preferred substrate of 4CL5, increased in line with significant upregulation of caffeoyl shikimate esterase1. Upregulation of caffeoyl-CoA O-methyltransferase1 and downregulation of F5Hs are consistent with preferential funneling of 4CL5 products toward G-lignin biosynthesis at the expense of S-lignin. Thus, transcriptional and metabolic adaptations to 4CL1-knockout appear to have enabled 4CL5 catalysis at a level sufficient to sustain lignification. Finally, genes involved in sulfur assimilation, the glutathione-ascorbate cycle and various antioxidant systems were upregulated in the mutants, suggesting cascading responses to perturbed thioesterification in lignin biosynthesis. One sentence summaryKnockout of lignin-associated 4CL1 in Populus reveals a 4CL5-dependent, caffeate-modulated compensatory pathway for lignification with links to thiol redox balance and sulfur assimilation.

plant biology↗