Biology subjects

Seiliez, I.

Publications and source records attributed to Seiliez, I..

4 recordsLinked to original sources

bioRxiv2024

Dissecting the nutritional regulations of a whole amino acid transporter family from a complex genome species: A holistic approach turning weaknesses into strengths

Amino acid transporters (AATs) are described as pivotal in maintaining circulating and cellular concentrations of AA via regulation of their expression in response to the cellular environment. Rainbow trout (RT), a complex genome species, is poorly described for AATs roles in controlling its predominant AA-based metabolism, despite representing a major challenge in the aquaculture nutrition field. Therefore, we identified the whole repertoire of AAT found in RT genome (>200), its expression in tissues and its nutritional regulations in vitro. Results garnered revealed the existence of different clusters of AATs, notably due to promoters bearing ATF4-related AA response elements. Moreover, the modeling of each AAT-specific cluster activities disclosed mTOR-related signaling functions of Ile and Phe, yet unknown in RT. Thus, this novel approach herein described should help to better grasp AA homeostasis in most organisms and topics such as fish nutrition and evolution.

cell biology↗

bioRxiv2024

The zebrafish as a new model for studying chaperone-mediated autophagy unveils its role in spermatogenesis

Chaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis involved in numerous cellular processes, and whose dysfunction is associated to several pathologies. Initially studied in mammals and birds, recent findings have identified CMA in fish, reshaping our understanding of its evolution across metazoans. Given the exciting perspectives this finding offered, we have now developed the required tools to investigate and functionally asses that CMA function in a powerful fish genetic model: the zebrafish (Danio rerio). After adapting and validating a fluorescent reporter (KFERQ-Dendra2; previously used to track CMA in mammalian cells) in zebrafish primary embryonic cells, we first demonstrated CMA functionality in this fish species. Then, we developed a transgenic zebrafish line expressing the KFERQ-Dendra2 CMA reporter, enabling the real-time tracking of CMA activity in vivo. This model revealed heterogeneous CMA responses within tissues, highlighting the zebrafish as a valuable model for investigating tissue-specific and cell-scale variations in CMA. Moreover, a novel role for CMA has been uncovered, acting as a gatekeeper of sperm cell proteostasis, thereby playing a crucial role in the production of active and high-quality spermatozoa. Overall, these findings emphasize the zebrafish as a pivotal model for advancing our comprehension of the fundamental mechanisms underlying CMA.

cell biology↗

bioRxiv2024

Chaperone-Mediated Autophagy in Fish: A Key Function Amid a Changing Environment

Chaperone-Mediated Autophagy (CMA) is a major pathway of lysosomal proteolysis critical for cellular homeostasis and metabolism. While extensively studied in mammals, CMAs existence in fish has only been confirmed recently, offering exciting insights into its role in species facing environmental stress. Here, we shed light on the existence of 2 genes encoding the CMA-limiting factor Lamp2A (lysosomal associated membrane protein 2A) in rainbow trout (RT, Oncorhynchus mykiss), revealing distinct expression patterns across various tissues. Notably, RT lacking the most expressed Lamp2A exhibit profound hepatic proteome disturbances during acute nutritional stress, underscoring its pivotal role as a guardian of hepatic proteostasis. Building upon these findings, we introduce and validate the CMA activation score as a reliable indicator of CMA status, providing a valuable tool for detecting cellular stress in fish under environmental threats. Overall, our study offers new perspectives into understanding CMA from evolutionary and environmental contexts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/585855v1_ufig1.gif" ALT="Figure 1"> View larger version (10K): org.highwire.dtl.DTLVardef@de3c56org.highwire.dtl.DTLVardef@4b711forg.highwire.dtl.DTLVardef@efb4a1org.highwire.dtl.DTLVardef@13be9cc_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Kinetic study of the expression of genes related to hepatic steatosis, global intermediate metabolism and cellular stress during overfeeding in mule ducks

Induced by overfeeding, hepatic steatosis is a reversible process exploited for \"foie gras\" production. To better understand the mechanisms underlying this non-pathological phenomenon, we analysed the physiological responses of the mule duck to cope with 22 carbohydrate meals. A kinetic analysis of intermediate metabolism and cell protection mechanisms was performed during overfeeding. As expected, dietary carbohydrates are up taken mainly by the liver (chrebp, glut1/2/8) and converted into lipids (acox, scd1, acsl1, fas, dgat2). Our study showed an activation of cholesterol biosynthetic pathway with significant correlations between plasma cholesterol, expression of key genes (hmgcr, soat1) and liver weight. Results revealed an activation of insulin and amino acid cell signalling pathway suggesting that ducks boost insulin sensitivity to raise glucose uptake and use via glycolysis and lipogenesis. Expression of cpt1a, acad, hadh suggested an induction of beta-oxidation probably to remove part of newly synthesized lipids and avoid lipotoxicity. Cellular stress analysis revealed an upregulation of autophagy-related gene expression (atg8, atg9, sqstm1) in contrast with an induction of cyp2e1 suggesting that autophagy could be suppressed. Lamp2a and plin2 enhanced, conflicting with the idea of an inhibition of lipophagy. Hsbp1 overexpression indicated that mechanisms are carried out during overfeeding to limit cellular stress and apoptosis to prevent the switch to pathological state. Atf4 and asns overexpression reflects the nutritional imbalance during overfeeding. These results permitted to highlight the mechanisms enabling mule ducks to efficiently handle the huge starch overload and reveal potential biomarker candidates of hepatic steatosis as plasma cholesterol for liver weight.

physiology↗