bims-toxgon 2026-06-14 papers

Issue of 2026–06–14
three papers selected by
Lakesh Kumar, BITS Pilani

Transbound Emerg Dis. 2026 ;2026 4901030

ATG5 Plays a Role in Toxoplasma gondii Replication and Egress Within Host Cells.

Fei Wu, Shanghua Wu, Qiying Ding, Zhiqiang Shi, Yinlong Liang, Hongchao Chen, Xiang Zhang, Jiawei Mi, Muxin Chen, Qianming Xu.

Toxoplasma gondii, an intracellular parasite with a global distribution, causes toxoplasmosis, resulting in significant economic losses. Drug resistance and vaccine deficiency have spurred interest in identifying novel intervention targets, including autophagy and autophagy-related proteins (ATGs). ATG5 is an important member of ATGs that plays a crucial role in disrupting the T. gondii parasitophorous vacuole membrane (PVM). However, its effects on the parasite's intracellular lifecycle warrant further investigation. In this study, the transgenic Vero cells were constructed using a lentivirus-mediated ATG5 overexpression or knockdown, which was used to evaluate the effects of ATG5 on T. gondii infection in vitro. The proliferation and development of the parasites in host cells were observed, and the number of parasitophorous vacuole (PV), pseudocysts, and lysed cells during various hours postinfection was counted under an optical microscope after Wright-Giemsa staining. The relative mRNA level of PTEN-induced putative kinase 1 (PINK1) in infected cells was detected using a real-time quantitative PCR (RT-qPCR). The mitochondrial membrane potential (MMP) of T. gondii tachyzoites was evaluated with a JC-1 fluorescence probe. The results showed that overexpressing ATG5 in Vero cells accelerated the invasion and egress processes of T. gondii tachyzoites and enhanced their proliferation compared to negative controls (NCs). Additionally, the mRNA level of PINK1 was upregulated in ATG5-overexpressing cells. Crucially, ATG5 overexpression induced MMP depolarization in the parasites, probably leading to their mitochondrial dysfunction. These findings were corroborated by ATG5-knockdown experiments, which yielded contrasting results. Collectively, ATG5 may have mediated premature parasite egress and mitochondrial damage, demonstrating its antiparasitic activity and therapeutic potential in controlling toxoplasmosis.

Keywords: ATG5; Toxoplasma gondii; host–parasite interaction; mitochondrial dysfunction; premature

DOI: https://doi.org/10.1155/tbed/4901030

Commun Biol. 2026 Jun 08.

Microtubule lattice conformation and integrity regulate α-tubulin acetylation.

Cornelia Egoldt, Marie-Claire Velluz, Joshua Tran, Charlotte Aumeier.

Microtubule acetylation of lysine 40 of α-tubulin is a hallmark of stable microtubules. This luminal modification is catalyzed by α-tubulin acetyltransferase 1 (αTAT1) and reversed by histone deacetylase 6 (HDAC6). However, acetylation regulation within the microtubule lumen and the influence of lattice architecture on enzymatic activity remain poorly understood. Here, we reconstitute microtubule acetylation in vitro using purified αTAT1 and HDAC6 on microtubules assembled with defined lattice conformations. We show that αTAT1 outweighs HDAC6 enzymatic activity, but its acetylation efficiency decreases upon microtubule damage. Importantly, αTAT1 efficiently acetylates microtubules with expanded lattices, while compacted lattices impede its activity. Our findings reveal that both microtubule integrity and lattice conformation are critical regulators for αTAT1 enzymatic activity, suggesting that dynamic transitions between compacted/expanded and intact/damaged lattices modulate the acetylation pattern of microtubules in cells.

DOI: https://doi.org/10.1038/s42003-026-10157-4

Nat Commun. 2026 Jun 11.

Targeting SMC3 deacetylation synergizes with XPO1 inhibition to reprogram the epigenetic landscape and suppress NPM1-mutated acute myeloid leukemia.

Jianfeng Fu, Huilin Xu, Xinying Zhao, Mengge Gao, Yonglu Tian, Yingjun Chang, Xiaofeng Zheng.

Acute myeloid leukemia (AML) is a prevalent hematologic malignancy. Mutations in Nucleophosmin (NPM1c) is the most frequent genetic alterations in AML. However, the epigenetic regulatory mechanisms of this AML subtype remain unclear. The cohesin complex, regulated by the acetyltransferase ESCO2, orchestrates chromatin organization and regulates gene expression. Here, we show that loss of ESCO2 promotes the progression of NPM1-mutated AML by destabilizing cohesin and the NuRD complex on chromatin, thereby enhancing the expression of genes associated with leukemia self-renewal capacity. Pharmacological HDAC8 inhibition restores SMC3 binding and induces differentiation and apoptosis in NPM1-mutated AML cells. Simultaneously targeting HDAC8 and nuclear exporter XPO1 reverses aberrant epigenetic landscape and represses self-renewal gene expression induced by ESCO2 deficiency. The combined treatment effectively eliminates NPM1-mutated AML cell lines and primary human AML cells in vitro and in vivo. This study reveals an ESCO2 deficiency-induced aberrant epigenetic landscape via SMC3 hypoacetylation and identifies a potential therapeutic strategy for NPM1-mutated AML.

DOI: https://doi.org/10.1038/s41467-026-74343-y