Biology subjects

Codogno, P.

Publications and source records attributed to Codogno, P..

3 recordsLinked to original sources

bioRxiv2023

YAP-dependent autophagy is controlled by AMPK, SIRT1 and flow intensity in kidney epithelial cells.

Shear stress generated by the urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy machinery in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirmed the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating the pathological flow observed at early stages of chronic kidney disease (CKD) activated YAP, leading to a primary cilium-dependent inhibition of autophagy. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD.

cell biology↗

bioRxiv2020

Epidermal stem cell compartment remains unaffected through aging in naked mole-rats.

Skin represents an informative and convenient organ for the analysis of the aging process. Naked mole-rats (NMR) are subterranean rodents remarkable for their longevity, with unexplained resistance to skin aging. In middle-aged NMR, extensive in situ analysis indicated that skin compartments and cell types remained similar to young animals. Using single-cell RNA-sequencing, we found three classical cellular states defining a unique keratinocyte differentiation trajectory that did not appear to be altered during aging after pseudotemporal reconstruction. Finally, NMR skin healing closure was strictly comparable between the two age groups. These results indicate that the content in stem cell populations as well as the differentiation process are preserved during aging in NMR and that such properties are related to the healing process.

cell biology↗

bioRxiv2020

p27 regulates the autophagy-lysosomal pathway via the control of Ragulator and mTOR activity in amino acid deprived cells

Autophagy is a catabolic process whereby cytoplasmic components are degraded within lysosomes, allowing cells to maintain energy homeostasis during nutrient depletion. Several studies have shown that the CDK inhibitor p27Kip1 promotes starvation-induced autophagy. However, the underlying mechanism remains unknown. Here, we report that in amino acid deprived cells, p27 controls autophagy via an mTORC1-dependent mechanism. During prolonged amino acid starvation, a fraction of p27 is recruited to lysosomes where it interacts with LAMTOR1, a component of the Ragulator complex required for mTORC1 lysosomal localization and activation. p27 binding to LAMTOR1 prevents Ragulator assembly and function and subsequent mTORC1 activation, thereby promoting autophagy. Conversely, upon amino acid withdrawal, p27-/- cells exhibit elevated mTORC1 signaling, impaired lysosomal activity and autophagy, and resistance to apoptosis. This is associated with sequestration of TFEB in the cytoplasm, preventing the induction of lysosomal genes required for lysosomal function. Silencing of LAMTOR1 or mTOR inhibition restores autophagy and induces apoptosis in p27-/- cells. Together, these results reveal a direct, coordinated regulation between the cell cycle and cell growth machineries.

cell biology↗