bims-imesem 2026-06-14 papers

Issue of 2026–06–14
four papers selected by
Akshara Kulkarni , University of Cambridge

Stem Cell Reports. 2026 Jun 11. pii: S2213-6711(26)00162-1. [Epub ahead of print] 102951

Electron transport chain complex I and mitochondrial fusion regulate ROS for differentiation in Drosophila neural stem cells.

Rahul Kumar Verma, Atharva Bhingare, Dnyanesh Dubal, Richa Rikhy.

Mitochondrial fusion and electron transport chain complex I are each essential for differentiation in Drosophila neuroblasts, but the mechanism by which they interact to mediate differentiation is unknown. We found that complex I subunit depletion did not affect type II neuroblast numbers but reduced their proliferation and decreased their lineage cells. Complex I depletion decreased the mitochondrial membrane potential and cristae numbers, increased fragmentation and ROS, and inhibited Notch signaling in lineage cells. Similarly, antioxidant enzyme depletion increased ROS and reduced lineage cells. Both complex I and antioxidant proteins promoted the G1/S transition and nuclear cyclin E levels. Additional mitochondrial fusion via Drp1 mutants restored ROS levels, proliferation, and differentiation defects in complex I and antioxidant protein-depleted neuroblasts. Overexpression of antioxidant proteins and an increase in Notch signaling alleviated ROS and the complex I depletion-driven defect in neuroblast proliferation and differentiation. Complex I and mitochondrial fusion together restrict ROS to support neuroblast proliferation and differentiation.

Keywords: Drosophila; Drp1; Notch; complex I; differentiation; mitochondria; mitochondrial fragmentation; mitochondrial fusion; neural stem cells; neuroblasts

DOI: https://doi.org/10.1016/j.stemcr.2026.102951

Nat Cell Biol. 2026 Jun 11.

DRP1 and MID49 co-diffusion scans mitochondria for fission.

Cristiana Zollo, David Gomez Suarez, Elmira Parvindokht Bararpour, Andreas Jenner, Pratima Verma, Jan Koch, Sabine Wilhelm, Christian Jüngst, Lukas Faber, Faye White, Ana J García-Sáez.

DRP1 is a dynamin-related large GTPase responsible for mitochondrial fission, which ensures proper mitochondrial distribution, morphology and quality control. Despite its relevance, the mechanism of mitochondrial division, especially regarding the dynamic regulation of DRP1, remains elusive. Here we report that DRP1 oligomers diffuse in helical-like trajectories along mitochondria, browsing the organelle surface and stalling at preconstricted fission sites, in what we call 'mito-scanner' motion. Molecular dynamics simulations support a geometry-mediated diffusion mechanism emerging from surface confinement. Perturbation of DRP1 motility results in elongated mitochondria, underscoring the functional importance of DRP1 scanning dynamics in mitochondrial division. We also show that DRP1 dynamics on mitochondria are differentially regulated by interactions with its adaptors, where co-diffusion of MID49/MID51 with DRP1 promotes its motility. Our findings support a model in which receptor-regulated mitochondrial surveillance by DRP1 enables balanced organelle division, with potential implications for targeting this process in disease.

DOI: https://doi.org/10.1038/s41556-026-01986-w

Sci Signal. 2026 Jun 09. 19(941): eadz1593

Cyclin-dependent kinase CDK1 targets cell-cell junction components and governs epithelial monolayer integrity throughout the cell cycle.

Margarida Dantas, Lisa Donker, Willem-Jan Pannekoek, Marjolein J Vliem, Jan A van der Beek, Robert M van Es, Harmjan R Vos, Judith Klumperman, Martijn Gloerich.

The cyclin-dependent kinase CDK1 is a master regulator of cell cycle progression and the associated changes in cell shape. The biochemical functions of CDK1 have been primarily studied in cultured cells lacking adhesion to their neighbors. Within epithelial layers, cells are tightly connected, and cell cycle-associated shape changes must occur without compromising epithelial barrier function. Here, we showed that a pool of CDK1 localized to cell-cell contacts in cultured epithelial cells and phosphorylated substrates at cell-cell junctions throughout the cell cycle. CDK1 substrates identified by proteomic analysis included various components of adherens junctions, tight junctions, and desmosomes, as well as proteins that link cell-cell adhesion complexes to the actomyosin cytoskeleton. CDK1 activity maintained the linear organization of cell-cell junctions and was essential for preserving the integrity of the epithelial barrier. These findings expand the role of CDK1 to the regulation of cell-cell adhesion, establishing that the machinery that governs the cell cycle also controls epithelial integrity.

DOI: https://doi.org/10.1126/scisignal.adz1593

Front Immunol. 2026 ;17 1742866

In vitro generation of RORγt+ regulatory T cells reveals enhanced immunosuppressive function and OXPHOS-dependent metabolism.

Marcella Cipelli, Eloísa Martins da Silva, Lais Cavalieri Paredes, Mariana Abrantes do Amaral, Barbara Nunes Padovani, Luísa Menezes-Silva, Vinicius Andrade-Oliveira, Niels Olsen Saraiva Camara.

Background: RORγt+ regulatory T cells (Treg) play a crucial role in immune regulation, particularly in the gut. However, most current knowledge about this subset derives from in vivo studies, as in vitro investigation has been limited by the lack of protocols capable of preserving their phenotype.
Methods: Here, we developed and optimized an in vitro differentiation protocol to efficiently generate RORγt+ Treg cells. The protocol was evaluated based on the frequency of RORγt+ Treg cells generated, their suppressive function compared to conventional induced Treg (iTreg), and their metabolic profile.
Results: The optimized protocol increased the frequency of RORγt+ Treg cells in vitro by up to 70%, providing a robust system for their study. Functionally, in vitro-differentiated RORγt+ Treg cells displayed enhanced immunosuppressive activity compared to conventional iTreg, effectively inhibiting effector CD4⁺ T cell proliferation. Metabolic analyses further revealed a reliance on oxidative phosphorylation (OXPHOS) in this subset.
Conclusion: This protocol enables the efficient in vitro generation of RORγt+ Treg cells, facilitating functional and metabolic studies of this population and opening new avenues for potential therapeutic applications in immune-mediated diseases.

Keywords: RORγt; T cell differentiation; T cell function; Treg; immunometabolism

DOI: https://doi.org/10.3389/fimmu.2026.1742866