Biology subjects

Vanacker, H.

Publications and source records attributed to Vanacker, H..

3 recordsLinked to original sources

bioRxiv2026

Antagonistic functions of the two oxidative pentose phosphate pathway dehydrogenases in shaping oxidative stress responses

The oxidative pentose phosphate pathway (OPPP) is a source of cellular NADPH, generated through the sequential activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH). Using the catalase-deficient cat2 background as a model for H2O2-triggered salicylic acid (SA) signaling we identified the cytosolic G6PDH isoform G6PD5 as a key determinant of redox homeostasis and SA-dependent defense activation (Tremulot et al., companion manuscript). However, the mechanisms underlying this function remain enigmatic. In this work, genetic and transcriptomic analyses show that the role of G6PD5 cannot be explained solely by altered NADPH generation for either NADPH oxidases or the ascorbate-glutathione pathway, suggesting other possible links. To identify such links, a forward genetic screen was employed. We searched for mutations that modulate the suppressed lesion phenotype in cat2 g6pd5 in a photorespiration-dependent manner. This screen identified a mutation in PGD2, encoding the cytosolic 6PGDH. Strikingly, functional analyses of mutants and overexpression lines revealed that PGD2 exerts effects opposite to those of G6PD5 in SA signaling. Our observations uncover an unexpected antagonism between the two cytosolic NADPH-producing steps within the OPPP. Pharmacological analyses support a signaling role for the metabolic intermediate 6-phosphogluconolactone in linking the OPPP to SA signaling. These findings indicate that the OPPP is not solely a source of reducing power during oxidative stress but also acts as a signaling module in which metabolic intermediates contribute to the control of stress-induced immune responses.

plant biology↗

bioRxiv2025

Oncogenic Stress is a Novel Immunogenic Signal Driven by the Unfolded Protein Response and Detected by Neutrophils

Breast cancer (BC) is the leading cause of cancer-related death in women. However, early detection of BC remains a major clinical challenge and represents a significant obstacle to effective prevention. To improve early clinical management, a deeper understanding of the preneoplastic immune microenvironment of BC is crucial. Among innate immune populations, neutrophils have emerged as important modulators of tumor development, but their role during the initiation of BC remains poorly understood. By integrating depletion experiments with transcriptomic profiling of sorted preneoplatic epithelial cells and neutrophils in spontaneous breast cancer mouse models, we observed that neutrophils contribute to tumor surveillance of preneoplastic stage with the activation of the unfolded protein response (UPR) in the preneoplastic epithelial compartment. To decipher the early anti-tumoral role of neutrophil, we developed an in vitro co-culture model of human mammary epithelial cells undergoing oncogenic stress with activation of the UPR (eHMEC), with human primary neutrophils. eHMEC display an immunoactive secretome as well as immunogenic membrane ligands, and neutrophils are the only immune cell population detecting eHMEC immunogenic signals leading to their recruitment, activation, production of reactive oxygen species and degranulation. Altogether, our work identifies for the first-time neutrophils as the earliest immune cell involved in immunosurveillance of preneoplastic BC epithelial cells, paving the way for potential therapeutic approaches targeting neutrophils to intercept early steps of BC tumorigenesis.

immunology↗

bioRxiv2023

A complex and dynamic redox network regulating oxygen reduction at photosystem I

Thiol-dependent redox regulations of enzyme activities play a central role in regulating photosynthesis. Beside the regulation of metabolic pathways, alternative electron transport has been shown to be subjected to thiol-dependent regulation. We investigated the regulation of O2 reduction at photosystem I. The level of O2 reduction in leaves and isolated thylakoid membranes depends on the photoperiod in which plants are grown. We used a set of Arabidopsis mutant plants affected in the stromal, membrane and lumenal thiol network to study the redox protein partners involved in regulating O2 reduction. Light-dependent O2 reduction was determined in leaves and in thylakoids of plants grown in short day and long day conditions using a spin-trapping EPR assay. In wild type samples from short day, ROS generation was twice the amount of that in samples from long day, while this difference was abolished in several redoxin mutants. An in vitro reconstitution assays showed that thioredoxin m, NADPH-dependent reductase C (NTRC) and NADPH are required for high O2 reduction levels in long day thylakoids. Using isolated photosystem I, we also show that reduction of a PSI protein is responsible for the increase in O2 reduction. Furthermore, differences in the membrane localization of thioredoxins m and 2-Cys peroxiredoxin were demonstrated between thylakoids of short day and long day plants. Finally, we propose a model of redox regulation of O2 reduction according to the reduction power of the stroma and the capabilities of the different thiol-containing proteins to form a network of redox interactions.

biochemistry↗