Biology subjects

Franke, R.

Publications and source records attributed to Franke, R..

7 recordsLinked to original sources

bioRxiv2025

Itaconate is metabolized to 2-hydroxymethylsuccinate through a CoA-independent degradation pathway in mitochondria

The immunometabolite itaconate modulates cellular metabolism and is converted into structurally similar C5 dicarboxylates that require advanced analytics to decipher their metabolic fate. Here, we employ high-resolution mass spectrometry and tracing approaches and identify 2-hydroxymethylsuccinate (2HMS) as a previously unrecognized C5 dicarboxylate derived from itaconate. 2HMS synthesis occurs during inflammatory responses and upon itaconate treatment, as detected by 13C itaconate tracing. Pathway analysis reveals that methylglutaconyl-CoA hydratase (AUH) drives 2HMS synthesis through a CoA-independent conversion (CIC) pathway. This pathway is distinct from the CoA-dependent conversion (CDC) pathway that generates mesaconate and itaconyl-CoA influencing B12-dependent processes. In vivo inflammation studies reveal that adipose tissue prefers CIC to produce 2HMS and liver favors CDC-mediated mesaconate synthesis, highlighting tissue-specific itaconate degradation routes. This study identifies a new branch of itaconate metabolism, provides an analytical framework to resolve C5 dicarboxylate networks, and links 2HMS to inflammation and mitochondrial metabolism that might be targeted therapeutically.

cell biology↗

bioRxiv2025

Metabolic reprogramming of methylthioadenosine-dependent sulfur recycling is a major driver of CHIKV infection

The supply of key metabolites into viral replication compartments must be assured through a coordinated reprogramming of host metabolic pathways. For chikungunya virus (CHIKV), the cellular metabolites required for a successful infection are largely unknown. We show that CHIKV reprograms sulfur-dependent pathways. To maintain the resupply of thiols, the methionine (Met) salvage players, 5'-methylthioadenosine (MTA) and methionine adenosyltransferase-2a (Mat2a) are co-induced specifically. Under sulfur-depleted conditions, exogenously added MTA restores CHIKV replication more efficiently than its precursor S-adenosylmethionine, while inhibitions of Mat2a or de novo cysteine (Cys) biosynthesis reduce viral infectivity. Upon sulfur insufficiency CHIKV upregulates the U34-tRNA methyltransferase ALKBH8, and when ALKBH8 is deleted, virus replication is reduced by impairing sulfur relay, recapitulating Met-Cys deprivation effects. We found that MTA-mediated CHIKV replication occurs via m6A-independent priming, and that the S-adenosylhomocysteine hydrolase inhibitors DzNep and Adox, inhibited CHIKV replication with nanomolar potency. Our findings uncovered a major pro-CHIKV metabolic rheostat regulating tRNA modifications that can be targeted with host-directed antiviral agents.

microbiology↗

bioRxiv2025

ABA-induced MYB transcriptional module regulates the differentiation trajectory of chickpea exodermis

Abscisic acid (ABA) regulates plant responses to stress and influences the differentiation of root barrier cell types, such as the endodermis and exodermis. Despite the importance of the exodermis in limiting water and solute fluxes, its regulation remains poorly understood in legumes. Here, we characterize the ABA-induced suberization and lignification of root tissues across eight galegoid legumes to identify exodermis-forming species in the clade. Chickpea deposited suberin lamella specifically in the outermost cortex and formed a functional apoplastic barrier, i.e. an exodermis. Transcriptomics of chickpea roots revealed ABA-induced programs that were temporally separated, specifically, a rapid program with the general ABA response, and a delayed programs of suberin and lignin biosynthesis. We identified WRKY and MYB transcription factors that putatively link the ABA response to the suberin biosynthesis, and using single-cell RNA-seq of chickpea roots we inferred an exodermis-expressed WRKY-MYB regulatory unit upstream of the suberin biosynthetic genes. Transactivation assays supported an ABA-dependent transcription factor activity upstream of suberin biosynthesis pathway in chickpea. Our results reveal a cell-type specific transcription factor hierarchy that coordinates hormone perception into an important mechanism of root plasticity in legumes.

plant biology↗

bioRxiv2024

Temperature-dependent polar lignification of a seed coat suberin layer promoting dormancy in Arabidopsis thaliana

The seed is a landmark plant adaptation where the embryo is sheltered by a protective seed coat to facilitate dispersion. In Arabidopsis, the seed coat, derived from ovular integuments, plays a critical role in maintaining dormancy, ensuring germination occurs during a favorable season. Dormancy is enhanced by cold temperatures during seed development by affecting seed coat permeability through changes in apoplastic barriers. However, the localization and composition of these apoplastic barriers are poorly understood. This study identifies and investigates a polar barrier in the seed coats outer integument (oi1) cells. We present histological, biochemical, and genetic evidence showing that cold promotes polar seed coat lignification of the outer integument 1 (oi1) cells and suberization throughout the entire oi1 cell boundary. The polar oi1 barrier is regulated by the transcription factors MYB107 and MYB9. MYB107, in particular, is crucial for the lignified polar oi1 barrier formation under cold temperatures. The absence of the oi1 barrier in mutant seeds correlates with increased permeability and reduced dormancy. Our findings elucidate how temperature-induced modifications in seed coat composition regulate dormancy, highlighting the roles of suberin and lignin in this process. Significance statementOur study uncovers how cold temperatures during seed development in the mother plant influence seed dormancy through apoplastic modifications in the Arabidopsis thaliana seed coat. We identified a polar lignin barrier in the outer integument 1 (oi1) cells, which are also suberized. Lignification and suberization are regulated by transcription factors MYB107 and MYB9. Cold promotes lignification and suberization of oi1 cells through MYB107, thus creating a "memory" that reduces seed permeability and strengthens dormancy. Mutants defective in the oi1 barrier exhibit lower dormancy, highlighting the adaptive importance of this barrier. These findings advance our understanding of temperature-induced seed coat adaptations and their agricultural implications, particularly in the context of climate change, offering valuable insights for improving crop resilience and yield.

plant biology↗

bioRxiv2021

Regulation of suberin biosynthesis and Casparian strip development in the root endodermis by two plant auxins

The biological function of the auxin phenylacetic acid (PAA) is not well characterized in plants. Although some aspects of its biology; transport, signaling and metabolism have recently been described. Previous work on this phytohormone has suggested that PAA behaves in an identical manner to IAA (indole-3-acetic acid) in promoting plant growth, yet plants require greater concentrations of PAA to elicit the same physiological responses. Here we show that normalized PAA treatment results in the differential expression of a unique list of genes, suggesting that plants can respond differently to the two auxins. This is further explored in endodermal barrier regulation where the two auxins invoke striking differences in the deposition patterns of suberin. We further show that auxin acts antagonistically on Casparian strip (CS) formation as it can circumvent the CS transcriptional machinery to repress CS related genes. Additionally, altered suberin biosynthesis reduces endogenous levels of PAA and CS deficiency represses the biosynthesis of IAA and the levels of both auxins. These findings implicate auxin as a regulator of endodermal barrier formation and highlight a novel role for PAA in root development and differentiation.

plant biology↗

bioRxiv2020

Spatio-temporal control of phenylpropanoid biosynthesis by inducible complementation of a cinnamate 4-hydroxylase mutant

Cinnamate 4-hydroxylase (C4H) is a cytochrome P450-dependent monooxygenase that catalyzes the second step of the general phenylpropanoid pathway. Arabidopsis reduced epidermal fluorescence 3 (ref3) mutants, which carry hypomorphic mutations in C4H, exhibit global alterations in phenylpropanoid biosynthesis and have developmental abnormalities including dwarfing. Here we report the characterization of a conditional Arabidopsis C4H line (ref3-2pOpC4H), in which wild-type C4H is expressed in the ref3-2 background. Expression of C4H in plants with well-developed primary inflorescence stems resulted in restoration of fertility and the production of substantial amounts of lignin, revealing that the developmental window for lignification is remarkably plastic. Following induction of C4H expression in ref3-2pOpC4H, we observed rapid and significant reductions in the levels of numerous metabolites, including several benzoyl and cinnamoyl esters and amino acid conjugates. These atypical conjugates were quickly replaced with their sinapoylated equivalents, suggesting that phenolic esters are subjected to substantial amounts of turnover in wild-type plants. Furthermore, using localized application of dexamethasone to ref3-2pOpC4H, we show that phenylpropanoids are not transported appreciably from their site of synthesis. Finally, we identified a defective Casparian strip diffusion barrier in the ref3-2 mutant root endodermis, which is restored by induction of C4H expression. HighlightThe work presented this paper provides evidence of metabolite turnover, plasticity of the developmental window for lignification, and the impact of reduced and restored cinnamate-4-hydroxylase (C4H) expression on the Casparian strip.

biochemistry↗

bioRxiv2020

Tissue-autonomous phenylpropanoid production is essential for establishment of root barriers

Plants deposit polymeric barriers in their root cell walls to protect against external stress and facilitate selective nutrient uptake. The compounds that make up these barriers originate from the fatty acid- and phenylpropanoid biosynthetic pathways. Although the machinery responsible for production of the barrier constituents is well-char-acterized, our pathway models lack spatiotemporal resolution - especially in roots - and the source tissue is often not clear due to the apoplastic nature of barriers. Insights into how the individual root tissues or cells contribute to forming apoplastic barriers is important for elucidation of their ultrastructure, function and development. Manipulation of the associated biosynthesis is delicate, as mutants often display pleiotropic phenotypes due to the broad role of the underlying metabolites. Here, we address these issues by creating a genetic tool that allows in vivo repression of the phenylpropanoid pathway with both spatial and temporal control. We provide strong evidence that tissue-auton-omous production of phenylpropanoids is essential for establishment of the endodermal Casparian strip. Moreover, we find that in order to maintain deposition and attachment of a coherent suberin matrix to the cell wall, cells require continuous production of aromatic constituents. This process is especially crucial in the suberized endodermis where we find that repression of phenylpropanoid production leads to active removal of suberin.

plant biology↗