bims-nocaut 2026-08-23 papers

Issue of 2026–08–23
three papers selected by
Quentin Frenger, University of Strasbourg

iScience. 2026 Aug 21. 29(8): 116866

Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.

Erin M Smith, Natali L Chanaday, Sandra Maday.

Lysosomal damage impairs proteostasis and contributes to neurodegenerative diseases, yet cell-type-specific differences in lysosomal repair remain unclear. Using a neuron-astrocyte coculture system, we compared responses to lysosomal injury induced by a lysosomotropic methyl ester. Both neurons and astrocytes showed lysosomal damage, marked by Galectin-3 recruitment to lumenal lysosomal β-galactosides, disrupted lysosomal pH, and engagement of lysophagy receptors TAX1BP1 and p62. However, astrocytes showed a preferential recruitment of ESCRT (endosomal sorting complex required for transport) repair machinery to damaged lysosomes. Additionally, the lysosomal membrane reformation pathway regulated by the RAB7-GTPase-activating protein (GAP), TBC1D15, was more robustly activated in astrocytes. By contrast, the phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway, mediating lipid transfer between the endoplasmic reticulum (ER) and damaged lysosomes, was engaged in both cell types. Our data reveal a divergence in how neurons and astrocytes mobilize repair pathways to manage lysosomal damage. These data may reflect differences in lysosomal resilience between astrocytes and neurons and inform therapeutic strategies to correct lysosomal dysfunction in neurodegenerative diseases.

Keywords: ESCRT; LLOMe; ORP9; PI4K2A; TBC1D15; astrocyte; lysosomal damage; neuron

DOI: https://doi.org/10.1016/j.isci.2026.116866

Immunity. 2026 Aug 17. pii: S1074-7613(26)00316-X. [Epub ahead of print]

Canonical and noncanonical autophagy in immunity.

Vojo Deretic.

Canonical and noncanonical autophagic processes are integrated with innate and adaptive immunity and sterile or pathogen-induced inflammation. In canonical autophagy, double-membrane autophagosomes modified by ubiquitin-like ATG8 proteins in a process termed membrane atg8ylation sequester and eliminate intracellular targets such as invading microbes, defunct organelles, aggregates, and inflammatory molecules. Recently, a plethora of noncanonical processes that entail membrane atg8ylation of various intracellular organelles other than autophagosomes have been linked to immunity. This has led to confounding interpretations and conflation of diverse processes as autophagy. Here, we posit that these are divergent manifestations of a common ancestral homeostatic process of membrane atg8ylation and provide an overview of how they affect immunity and inflammation. These relationships are evident in model organisms and are reflected in human genetic predispositions to diseases with immune components. The membrane atg8ylation pathways affect acute and chronic inflammation, infections, autoimmunity, cancer, neurodegeneration, metabolic syndrome, diabetes, and other disorders.

Keywords: autophagy; immunity; infection; membrane atg8ylation

DOI: https://doi.org/10.1016/j.immuni.2026.07.017

Autophagy. 2026 Aug 21. 1-10

Dealing with membrane stress through CASM.

Håvard Styrkestad Haukaas, Sven R Carlsson, Alf Håkon Lystad.

Compartments of the endolysosomal and secretory pathways encounter diverse insults - from loss of ion gradients and osmotic imbalance to physical membrane disruption - creating a need for rapid, localized surveillance and response systems. Recent work demonstrates that conjugation of ATG8 to single membranes (CASM) provides such specificity via stress-responsive targeting mechanisms that recruit the ATG8 conjugation machinery through pathways distinct from macroautophagy/autophagy. Here, we review recent advances in how membrane stress is sensed, coupled to CASM initiation, and converted into downstream cellular responses.

Keywords: ATG16L1; ATG16L2; ATG8; STIL; TECPR1; VAIL

DOI: https://doi.org/10.1080/15548627.2026.2717033