bims-nocaut 2025-09-21 papers

Issue of 2025–09–21
three papers selected by
Quentin Frenger, University of Strasbourg

Autophagy. 2025 Sep 17.

ATG8ylation-orchestrated vacuolar membrane remodeling facilitates plant alkaline stress tolerance.

Jianxiong Wu, Jun Luo, Chunya Nie, Xuanang Zheng, Caiji Gao, Jun Zhou.

While ATG8ylation, the C-terminal lipidation of mammalian and plant Atg8 (ATG8)-family proteins, is a well-established driver of autophagosome formation, emerging evidence reveals its non-canonical role in modifying single-membrane organelles under diverse environmental stresses. In a recent study, we found that disruption of the vacuolar proton gradient by alkaline stress rapidly triggers the translocation of ATG8 to the vacuolar membrane in plants. ATG8ylation facilitates membrane invagination through a mechanism independent of both ESCRT and the cytoskeleton. Concurrently, ATG8 recruits ATG2 to endoplasmic reticulum (ER)-vacuolar membrane contact sites, a process that may contribute to damaged membrane repair. Together, these processes enable plants to rapidly recover from vacuolar pH imbalance and adapt to alkaline conditions. Our findings advance the understanding of ATG8ylation in vacuolar membrane homeostasis and damage response, highlighting its conserved role in organellar stability and stress adaptation.

Keywords: ATG8ylation; Alkaline stress; monensin; non-canonical autophagy; vacuole

DOI: https://doi.org/10.1080/15548627.2025.2562885

J Cell Biol. 2025 Oct 06. pii: e202509030. [Epub ahead of print]224(10):

ATG16L strikes again! New findings link lysosome stress and physiology.

Alison D Klein, Michael Overholtzer.

Lysosome stress responses are emerging, but their connections to normal physiology are not well understood. In this issue, Duque et al. (https://doi.org/10.1083/jcb.202503166) discover that the autophagy protein ATG16L, a mediator of a stress response called CASM, also regulates normal lysosome function.

DOI: https://doi.org/10.1083/jcb.202509030

Autophagy. 2025 Sep 19.

Non-canonical role of ATG4B in PRMT1-mediated DNA repair and leukemia progression.

Zhenkun Wang, Yuting Fu, Shuyi Lin, Yuanyuan Zhou, Qiongdan Gao, YanHong Xiao, Zhenyu Ju, Bo Liu.

Accumulating evidence indicates that many ATG (autophagy related) proteins perform non-canonical functions beyond their canonical roles in autophagy, particularly when they localize to subcellular compartments outside the cytoplasm. Although the autophagic functions of ATG4B (autophagy related 4B, cysteine peptidase) are well established, its potential non-canonical roles, especially under metabolic stress, remain largely unexplored. In our recent study, we show that energy deprivation induces autophagy-independent nuclear translocation of ATG4B. In the nucleus, ATG4B interacts with and cleaves PRMT1 (protein arginine methyltransferase 1), thereby reducing PRMT1-mediated methylation of the DNA-repair nuclease MRE11 and consequently impairing DNA repair. Notably, ATG4B is significantly upregulated in acute myeloid leukemia (AML) and shows prominent nuclear accumulation. Genetic knockdown or pharmacological inhibition of ATG4B in AML cells restores DNA repair capacity, activates the cell-cycle checkpoint kinase CHEK1/CHK1, attenuates malignant progression, and ultimately delays leukemia progression. These findings reveal an autophagy-independent role for nuclear ATG4B that links metabolic stress to the suppression of DNA repair and identify ATG4B as a potential therapeutic target in AML.

Keywords: ATG4B; DNA repair; PRMT1; energy metabolism; leukemia

DOI: https://doi.org/10.1080/15548627.2025.2564225