Issues

Klein and Overholtzer discuss new findings from the Deretic group showing ATG16L, a regulator of lysosomal stress responses, has a day job regulating the v-ATPase.

Miller and Barmada discuss recent work from Hasegawa-Ogawa and colleagues, which reveals distinct mechanisms by which TDP43 and other ALS-associated RNA-binding proteins regulate the expression and activity of TDP43.

Huang and He discuss recent advances from Araujo Alves et al., describing how intraflagellar transport trains in Trypanosoma brucei selectively associate with axonemal doublet microtubules.

Tartier et al. summarized the ways biomolecular condensates have been purified in past years, highlighting common practices and challenges.

Henne and Prinz discuss the lipid droplet field and pervasive questions surrounding droplets and their roles in physiology and disease.

The authors show that TFEB is regulated by at least two different regulatory mechanisms during lysosomal damage: ATG conjugation system–dependent/independent regulation. The presence of two modes of regulation is further supported by the identification of novel regulators working in each mode.

Zheng et al. reveal that during starvation, SOD1, linked to ALS, is transported into lysosomes through autophagy and the receptor protein TP53INP1. Within lysosomes, SOD1 preserves its enzymatic function, regulating ROS levels and safeguarding lysosomal activity and integrity.

In Trypanosoma brucei, IFT trains selectively associate with specific axonemal microtubules. Using advanced microscopy, Araujo Alves et al. reveal how this restriction occurs at the proximal portion of the flagellum during the assembly and/or disassembly of IFT trains.

ch-TOG family proteins perform numerous microtubule regulatory functions. Abouelghar et al. show that budding yeast Stu2’s kinetochore function is essential for cell viability. Surprisingly, this function is independent of its canonical ability to induce microtubule assembly and disassembly.

Zhao et al. show that, in cancer cells using the ALT pathway, SUMO levels at telomeres influence the formation of APBs. Elevated SUMO levels promote the nucleation of PML bodies at telomeres instead of the fusion of telomeres with existing PML bodies, resulting in increased ALT activities.

Hasegawa-Ogawa et al. identify a dominant-negative TDP-43 isoform regulated by ALS-linked RNA-binding proteins. hnRNP K promotes its expression, while hnRNP A1 and FUS suppress it. ALS-mutant FUS weakens this regulation, potentially contributing to TDP-43 dysfunction in ALS pathogenesis.

In this study, Thompson et al. demonstrate that two cis-Golgi golgins, GMAP210 and Golgin-160, have distinct, nonredundant roles in maintaining Golgi organization and that both are required to support the efficient secretion, assembly, and modification of extracellular matrix proteins.

Shannon et al. show that the septin cytoskeleton localizes to mitochondrial fission sites to promote fission in an early, actin-dependent stage for mitochondrial calcium influx. Fission requires SEPTIN9 to activate a RhoGEF, ARHGEF18, and highlights the complexity of cytoskeletal regulation at an organelle interface.

Caballero et al. show that a polymorphism in the Mkt1 gene underlies complex genetic phenotypes among strains of budding yeast. Mkt1 interacts with a stress granule protein Pbp1 to regulate expression of mitochondrial proteins, TORC1 signaling, and autophagy in yeast.

During cortical astrocyte morphogenesis, mitochondria fragment and decrease in size to populate distal astrocyte processes. Drp1-mediated mitochondrial fission is necessary for peripheral astrocyte process formation. Astrocyte-specific Drp1 loss induces astrocyte reactivity, disrupts cortical astrocyte organization, and dysregulates PAP proteins, including gap junction protein connexin 43 abundance.

Duque et al. report a hitherto unappreciated function of ATG16L1, best known for its roles in canonical autophagy and membrane atg8ylation, in directly regulating V-ATPase, a key pump governing acidification and functionality of the endolysosomal system.

Insulin granule fusion localizes to where pancreatic β cells contact the ECM of the islet capillaries. Deng et al. report that liprin-α1 is part of a glucose-regulated complex controlling the positioning of insulin granule fusion. Our findings reveal a novel step in the mechanism of stimulus–secretion coupling.

This study by Alemany and Moore shows that Kip3/kinesin-8 requires the carboxy-terminal tail of beta-tubulin for depolymerase activity but not for binding or motility along microtubules. These results indicate that the beta-tubulin tail plays distinct roles the microtubule lattice vs the plus end or in solution.

Wang et al. reveal that multiple transmembrane proteins of the ciliary transition zone, including TMEM67, undergo core fucosylation. They show that FUT8-mediated core fucosylation stabilizes TMEM67 to promote ciliogenesis and that FUT8 deficiency in mice causes ciliary defects in multiple organs.

The kinesin-3 KIF1C forms condensates where the exposed kinesin motor domains entangle neighboring microtubules, causing them to bend and break. Geng et al. combine simulations and experiments to determine the microtubule rupture force and delineate the contributions of motor processivity, cluster properties, cytoplasmic viscosity, and microtubule anchors to microtubule breaking.

Losier et al. identify distinct kinase signaling pathways that differentially regulate bulk and selective autophagy. Using kinome-wide CRISPR screening, they reveal both shared and pathway-specific regulators, providing new insights into how cells tailor autophagy responses to selectively degrade damaged organelles under stress.

Padman et al. outline a segmentation strategy for 3D FIB-SEM data from cells, termed AIVE, which refines segmentation results from any AI-based method. Through AIVE, they discover a previously unknown category of mitochondrial contact that we term the mitochondrial intrusion.