Biology subjects

Serot, C.

Publications and source records attributed to Serot, C..

3 recordsLinked to original sources

bioRxiv2024

Reticulon dependent ER-phagy mediates adaptation to heat stress in Caenorhabditis elegans

The selective degradation of ER by autophagy, named ER-phagy, promotes the recovery of ER homeostasis after a stress. Depending on the ER stress, different types of ER-phagy involve various selective autophagy receptors. In this study, we report a macroER-phagy induced by the fragmentation of tubular ER in response to acute heat stress. We identified a novel ER-phagy receptor encoded by the reticulon long isoform RET-1d. RET-1d is mainly expressed in the nervous system and the epidermis and colocalize with the ubiquitin-like autophagy protein LGG-1/GABARAP during heat stress induced autophagy. Two LIR motifs in the long intrinsically disordered region of RET-1d mediate its interaction with LGG-1 protein. The specific depletion of RET-1d isoform resulted in a delay in autophagosome biogenesis and a decrease in the capacity of animals to adapt to heat stress. Our data revealed a RET-1d dependent ER-phagy mechanism that takes place in neurons and epidermis and participates to the adaptation of C. elegans to heat stress.

cell biology↗

bioRxiv2023

TLN468 changes the pattern of tRNA used to readthrough premature termination codons in CFTR

Nonsense mutations account for 12% of cystic fibrosis (CF) cases. The presence of a premature termination codon (PTC) leads to gene inactivation, which can be countered by the use of drugs stimulating PTC readthrough, restoring production of the full-length protein. We recently identified a new readthrough inducer, TLN468, more efficient than gentamicin. We measured the readthrough induced by these two drugs with different cystic fibrosis transmembrane conductance regulator (CFTR) PTCs. We then determined the amino acids inserted at the S1196X, G542X, W846X and E1417X PTCs of CFTR during readthrough induced by gentamicin or TLN468. TLN468 significantly promoted the incorporation of one specific amino acid, whereas gentamicin did not greatly modify the proportions of the various amino acids incorporated relative to basal conditions. The function of the engineered missense CFTR channels corresponding to these four PTCs was assessed with and without potentiator. For the recoded CFTR, except for E1417Q and G542W, the PTC readthrough induced by TLN468 allowed the expression of CFTR variants that were correctly processed and had significant activity that was enhanced by CFTR modulators. These results suggest that it would be relevant to assess the therapeutic benefit of TLN468 PTC suppression in combination with CFTR modulators in preclinical assays.

molecular biology↗

bioRxiv2021

Study of Metyltetraprole, an unusual agrofungicide targeting the Qo-site of cytochrome bc1 complex

The mitochondrial respiratory chain bc1 complex is a proven target of agrofungicides. Most of them are Qo-site antagonists (i.e QoIs), competing with the substrate ubiquinol, and likely share the same binding mode as the widespread Qo-site resistance mutation G143A confers cross-resistance. Metyltetraprole (MTP) presents an exception as studies with phytopathogenic fungi showed that the inhibitor was unaffected by G143A. Here, we used the yeast model to investigate its mode of action. Analysis of bc1 complex mutants supports a Qo-site binding for MTP. However the compound seems distinct to other QoIs, such as azoxystrobin, in various ways, namely; 1) G143A was without effect on MTP, as previously reported. 2) The level of MTP resistance of mutants was higher in bc1 complex activity assays than in growth assays while the opposite was observed with azoxystrobin. 3) Steady-state kinetics used to characterise the mode of action of MTP also revealed differences compared to other QoIs.

biochemistry↗