bims-mecosi 2026-10-04 papers

Issue of 2026–10–04
four papers selected by
Verena Kohler, Umeå University

Curr Biol. 2026 Oct 02. pii: S0960-9822(26)01198-X. [Epub ahead of print]

Mitochondria-ER-lipid droplet crosstalk regulates metabolic adaptation to shear stress via VMP1.

Maria Laura Rojas, Maribel Lara Corona, Carla Alemany, Juliane Da Graça, Nicolas Goudin, Ivan Nemazanyy, Ida Chiara Guerrera, Aurore Claude-Taupin, Etienne Morel.

Kidney tubular epithelial cells adapt to physiological urinary flow through rapid metabolic remodeling,1,2 but the mechanisms coordinating this response remain poorly understood. Shear stress promotes lipid catabolism and mitochondrial activity in these cells,3,4 but how changes in mitochondrial dynamics contribute to this metabolic adaptation remains poorly understood.5,6,7,8,9 Here, we show that physiological shear stress rapidly remodels mitochondrial morphology in kidney epithelial cells in vitro and in the zebrafish pronephros, characterized by the emergence of a distinct pool of donut-shaped mitochondria. This remodeling is accompanied by a transient stabilization of mitochondria-endoplasmic reticulum (ER) contact sites (MERCs), occurring independently of any increase in overall ER volume. Using split-TurboID proximity labeling and mass spectrometry, we detected subtle changes in the molecular environment of MERCs during shear stress, including increased proximity of proteins implicated in lipid transfer and membrane contact-site biology. We further show that shear stress promotes the formation of ER-lipid droplet (LD)-mitochondria contact sites and facilitates the local transfer of fatty acids from LDs to mitochondria. This lipid transfer requires vacuolar membrane protein 1 (VMP1), a component of membrane contact sites, whose depletion perturbs LDs and compromises metabolic adaptation to shear stress. Together, our findings identify ER-LD-mitochondria contact sites as dynamic platforms that coordinate lipid transfer and mitochondrial remodeling during the early adaptation of kidney epithelial cells to physiological shear stress, highlighting membrane contact sites as important components of the cellular response to mechanical forces.

Keywords: contact sites; endoplasmic reticulum; kidney epithelial cells; lipid droplets; metabolic adaptation; mitochondria; shear stress; zebrafish

DOI: https://doi.org/10.1016/j.cub.2026.09.021

Biol Cell. 2026 Oct;118(10): e70082

A Novel Striated Membrane Contact Site in Vestibular Hair Cells.

Nicolas Brouilly, Nathalie Pujol, Fabrice Richard, Chantal Cazevieille, Jennifer Stone, Ruth Anne Eatock, Rémy Pujol.

The mammalian vestibular system has two types of sensory receptor hair cells (HCs), each with different neurotransmission mechanisms. Type II HCs use ribbon synapses to transmit neurotransmitters like glutamate to bouton terminals of afferent neurons. Type I HCs are nearly engulfed by a calyceal afferent ending. They regulate afferent activity through both quantal and non-quantal transmission (NQT), the latter faster than classic neurotransmitter release and potentially key to stabilizing vision and balance during rapid head movements. Here, we describe a novel striated contact, present only in the mouse type I HC and its calyceal afferent ending. Electron tomography reveals periodic striations on both the HC and calyx plasma membranes. These contact sites are intimately associated with a plasma membrane mitochondria contact site on the type I HC side of the synapse. Given that mitochondrion-plasma membrane contact sites in other systems regulate local ion homeostasis, this distinctive arrangement has the potential to serve or modulate NQT at the type I HC-calyx synapse.

DOI: https://doi.org/10.1111/boc.70082

Aging Cell. 2026 Oct;25(10): e70738

Targeting Ero1L by Parthenolide Alleviates Cellular Senescence and Fibrosis of Localized Scleroderma by Regulating Mitochondria-Associated Endoplasmic Reticulum Membranes Stabilization.

Fei Wang, Ru Xing, Meijuan Xie, Yimin Qin, Yunchao Zhang, Dan Cao, Gu He, Xiaoyan Lyu.

Mitochondrial dysfunction drives scleroderma pathogenesis. The mitochondria-associated endoplasmic reticulum membrane (MAM) regulates mitochondrial function. Parthenolide (PTL) has protective effects on mitochondria. However, its specific role and mechanisms in localized scleroderma (LoS) remain unclear. This study investigates whether PTL reduces senescence and skin fibrosis by stabilizing MAM in LoS and examines the protective effects of a synthesized thermosensitive controlled-release hydrogel (F127@PLGA@PTL) against LoS. We employed transmission electron microscopy (TEM) to observe MAM abnormalities in LoS skin lesions. Other multiple molecular biology experiments were conducted to investigate how PTL protects against LoS in TGF-β-induced human dermal fibroblasts (HDFs) and a murine model of LoS. RNA sequencing, molecular docking-based inverse virtual screening, and surface plasmon resonance (SPR) were used to find possible targets of PTL. Emulsification-volatilization was used to prepare the PTL-loaded PLGA nanoparticles. MAM's calcium ion transport function is enhanced, and its quantity increases in LoS. PTL can ameliorate senescence and fibrosis in TGF-β-induced HDF cells and the bleomycin-induced LoS model by regulating the IP3R1/Grp75/VDAC1 complex and repairing mitochondrial damage. Notably, mechanistically, this protective effect was mediated through Ero1L suppression, with ARG-449 identified as the critical residue for PTL-Ero1L binding. Ero1L overexpression reversed the protective effects of PTL. Additionally, Ero1L knockdown also exhibits anti-senescence and antifibrotic effects on TGF-β-induced HDFs. Furthermore, F127@PLGA@PTL demonstrates excellent sustained-release properties and significant therapeutic efficacy in the mouse model of LoS. The study demonstrates that PTL alleviates fibrosis of LoS by regulating Ero1L-mediated MAM stabilization.

Keywords: Ero1L; cellular senescence; fibrosis; localized scleroderma; mitochondria associated‐endoplasmic reticulum membrane; parthenolide

DOI: https://doi.org/10.1111/acel.70738

Adv Sci (Weinh). 2026 Sep 30. e78067

The Cytoplasmic MicroRNA-Production Complex Regulates MicroRNA Sorting to Extracellular Vesicles During Synaptogenesis.

Yuzhou Zeng, Selina Luhmann, Aditi Saha, Marta Orlando, Haider Sami, Timo Glatter, Anna Antoniou.

Extracellular vesicles (EVs) have emerged as novel players of cell communication, in part via the transfer of microRNA (miRNA) cargo to recipient cells. Although several RNA-binding proteins (RBPs) were shown to shuttle miRNAs to EVs, how they are loaded with miRNA is unknown. This study demonstrates that the core accessory protein of the cytoplasmic miRNA production machinery TRBP interacts with several EV-RBPs and differentially regulates miRNA secretion in small EVs. TRBP-regulated EV-miRNAs were highly enriched in a Syncrip-recognition sequence motif. Moreover, we show that Syncrip associates with TRBP via its C-terminal domain at the surface of the endoplasmic reticulum (ER), a nucleation site of the miRNA production machinery. The recruitment of Syncrip to ER-associated TRBP was regulated by ER-endosome membrane contact sites (MCS), whereby increased MCS formation promotes Syncrip loading to endosomes as well as Argonaute 2-positive RNA granules. Functionally, this pathway is important for the regulation of synapse formation in developing neurons, as expression of miRNA- or TRBP-binding deficient mutants of Syncrip differentially regulated synapse formation in EV-donor and recipient neurons. Overall, this work highlights an important role of TRBP as a gatekeeper for microRNA sorting, which could be crucial for the fine-tuning of neuronal circuits during postnatal development.

Keywords: RNA granule; RNA‐binding protein; extracellular vesicle; microRNA sorting; organelle contact sites; synapse formation

DOI: https://doi.org/10.1002/advs.78067