bims-raghud 2026-03-15 papers

Issue of 2026–03–15
two papers selected by
Irene Sambri, TIGEM

Nat Cell Biol. 2026 Mar 13.

Time-resolved functional genomics using deep learning reveals global hierarchical control of autophagy.

Nathalia Chica, Aram N Andersen, Sara Orellana-Muñoz, Ignacio Garcia, Aurélie Nguéa P, Sigve Nakken, Pilar Ayuda-Durán, Linda Håkensbakken, Sebastian W Schultz, Eline Rødningen, Christopher D Putnam, Manuela Zucknick, Tor Erik Rusten, Jorrit M Enserink.

Recycling of cellular components through autophagy maintains homeostasis in changing nutrient environments. Although its core mechanisms are extensively studied, understanding of its systems-wide dynamic regulation remains limited, particularly regarding how autophagy is inactivated once nutrients are restored. Here we mapped the genetic network that controls activation and inactivation of autophagy during nitrogen changes by combining time-resolved high-content imaging, deep learning and latent feature analysis. This dataset, termed AutoDRY, categorizes 5,919 mutants based on nutrient response kinetics and their contributions to autophagosome formation and clearance. Integrating these profiles with functional and genetic network data uncovered hierarchical and multilayered control of autophagy and revealed multiple new regulatory pathways. Notably, we identified the retrograde pathway as a pivotal time-varying modulator that tunes the expression of core autophagy genes and plays a central role in autophagy inactivation. Together, this study establishes a systems-level resource to guide future investigations of autophagy.

DOI: https://doi.org/10.1038/s41556-025-01837-0

Int J Surg Pathol. 2026 Mar 13. 10668969251415520

FLCN-Mutated Tumors in Smith-Magenis Syndrome: A Case Report of FLCN-Associated Pathogenesis.

Émilie Pichette, Ali Shahini, Senthilkumar Kailasam, Simon Tanguay, William D Foulkes, Yasser Riazalhosseini, Fadi Brimo.

Birt-Hogg-Dubé syndrome and Smith-Magenis syndrome both involve the 17p11.2 chromosomal region, with FLCN germline pathogenic variants causing Birt-Hogg-Dubé syndrome and RAI1 deletions causing Smith-Magenis syndrome. When Smith-Magenis syndrome deletions extend to include FLCN, Birt-Hogg-Dubé syndrome-related manifestations may develop; however, such occurrences remain anecdotal, particularly with respect to renal tumors. We describe a 35-year-old man with Smith-Magenis syndrome who developed two right renal tumors, including one confirmed FLCN-mutated tumor. Histology revealed a mosaic admixture of oncocytic and chromophobe-like cells with patchy keratin 7 and KIT expression. Molecular analysis identified a germline 17p11.2 deletion encompassing FLCN and RAI1, together with a somatic FLCN splice-donor mutation (c.1300+1G>A), consistent with biallelic FLCN inactivation. These findings support a shared pathogenic mechanism between Smith-Magenis syndrome and Birt-Hogg-Dubé syndrome, contributing to the existing literature on FLCN-associated renal neoplasia. Recognition of this overlap is important for clinical awareness and further supports renal surveillance in Smith-Magenis syndrome patients.

Keywords: Birt-Hogg-Dube syndrome; FLCN; Smith-Magenis syndrome; chromosome 17 deletion; kidney neoplasms

DOI: https://doi.org/10.1177/10668969251415520