bims-mitrat 2026-02-22 papers

J Hazard Mater. 2026 Feb 14. pii: S0304-3894(26)00446-2. [Epub ahead of print]505 141468

Mechanism of macrophage mitochondrial transfer in CBNPs induced EndMT of pulmonary microvascular endothelial cells.

Mengruo Wang, Qian Wang, Qingping Liu, Shanshan Zhang, Yujia Xie, Tao Zhang, Ze Yang, Lei Bao, Yaxian Pang, Dongxing Shi, Jiaji Cheng, Yujie Niu, Zhihong Zhang, Rong Zhang.

Carbon black nanoparticles (CBNPs) have been identified as a potential contributing factor to idiopathic pulmonary fibrosis (IPF), though the specific mechanisms by which they induce endothelial-mesenchymal transition (EndMT) remain to be fully elucidated. The objective of this study was to ascertain whether CBNPs induce EndMT in pulmonary microvascular endothelial cells via PANoptosis-mediated mitochondrial transfer in alveolar macrophages (AMs). A mouse model of CBNPs inhalation exposure was established to evaluate pulmonary function, collagen deposition, and EndMT biomarkers. Co-culture systems of alveolar macrophages cells (M-HS) and pulmonary microvascular endothelial cells (MPVECs) were employed to investigate the process by which PANoptosis induced mitochondrial transfer. Key mechanisms were validated using Western blot, qPCR, molecular docking, co-immunoprecipitation, and bioinformatics analyses. The results showed that CBNPs exposure significantly impaired pulmonary function, induced collagen deposition, and activated EndMT. Conditioned media from CBNPs-treated M-HS triggered EndMT in MPVECs, mediated by the transfer of damaged mitochondria. Mechanistically, CBNPs suppressed the PINK1/Parkin mitophagy pathway, driving PANoptosis in M-HS and subsequent released of dysfunctional mitochondria. IFI27 was identified as a critical regulator of PANoptosis, directly binding to PINK1 to exacerbate mitochondrial dysfunction. Silencing IFI27 alleviated PANoptosis and mitochondrial transfer, reversing the EndMT phenotype in MPVECs. Collectively, these findings indicated that CBNPs induced EndMT in MPVECs via mitochondrial transfer, with the IFI27-PINK1 axis regulating this transfer process. This mitochondrial transfer represents as a novel therapeutic target for CBNPs-induced IPF. Moreover, modulating the process of mitochondrial transfer with IFI27 as a regulatory factor mitigate nanotoxicity-driven pulmonary fibrotic progression.

Keywords: Carbon black nanoparticles; Endothelial-mesenchymal transition; Mitochondrial transfer; PANoptosis; Pulmonary fibrosis

DOI: https://doi.org/10.1016/j.jhazmat.2026.141468

Neoplasia. 2026 Feb 14. pii: S1476-5586(26)00017-5. [Epub ahead of print]73 101288

SMARCA4 deficiency in glioblastoma: Mitochondrial transfer from MSCs and the clinical dilemma in targeting the tumor microenvironment.

Fan Yang, Lin Chen, Yuchen Shi, Lude Wang, Minfeng Tong.

INTRODUCTION: SMARCA4, a pivotal transcription activator regulating chromatin structure, gene expression, and cellular energy metabolism, has well-documented roles in various cancers. However, its specific function in glioblastoma (GBM) pathogenesis remains underexplored. This study investigates the correlation between SMARCA4 expression and GBM progression, with a focus on the tumor microenvironment.
MATERIALS AND METHODS: Single-cell RNA sequencing analyzed dynamic niche cell proportion shifts (e.g., mesenchymal stromal cells, MSCs) during GBM progression. SMARCA4 knockdown was executed in MSCs for in vitro functional evaluations, while an immunodeficient xenograft model was utilized to assess the impact of SMARCA4-deficient MSCs on in vivo GBM progression. Mechanistic studies focused on microtubule-dependent mitochondrial transfer in IDH mutant/wild-type tumors.
RESULTS: SMARCA4 was identified as a critical MSC regulator. Its knockdown altered MSC/GBM cell behavior in vitro, accelerated in vivo GBM progression, and worsened outcomes. SMARCA4-deficient MSCs enhanced GBM growth via mitochondrial transfer, altering MSC proliferative phenotype but increasing mitochondrial metabolic capacity.
DISCUSSION: Our findings highlight SMARCA4's critical role in regulating MSC function within the GBM microenvironment. Targeting SMARCA4-mediated mitochondrial transfer in MSCs may represent a novel therapeutic strategy for GBM.

Keywords: Glioblastoma; Mesenchymal stromal Cells; Mitochondria transfer; SMARCA4; Tumor micro-environment

DOI: https://doi.org/10.1016/j.neo.2026.101288

Adv Mater. 2026 Feb 15. e14070

High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis.

Fuxiao Wang, Hao Zhang, Dongyang Zhou, Xuan Tang, Jian Wang, Han Liu, Xiuhui Wang, Yuanwei Zhang, Zuhao Li, Yingying Jiang, Qin Zhang, Xiao Chen, Yingying Jing, Ke Xu, Yan Hu, Long Bai, Jiacan Su.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited therapeutic effectiveness of conventional biomaterials, which often lack targeted accuracy, delivery efficiency, and biocompatibility. Here, we present a biomimetically engineered carrier material using mitochondria as "living materials" to restore cell homeostasis in RA. The dual action carrier consists of a folic acid-modified macrophage membrane targeting activated M1 macrophages in RA joints, and it enables in situ mitochondrial transfer with more than twofold increase of delivery efficiency, which is a critical limitation of current approaches. By facilitating precise intracellular transfer of healthy mitochondria, and incorporating autophagy targeting chimera 4 (AUTAC4) in order to selectively destroy dysfunctional mitochondria, this design achieves complete mitochondrial renewal, increasing energy metabolism and homeostasis. In an RA model, the Dual-Action Mitochondrial Renewal Therapy (DAMRT) showed significant therapeutic potential. It could be used as a novel platform for treatment for RA and other mitochondrial dysfunction.

Keywords: AUTAC4; living material; macrophage reprogramming; mitochondrial transfer; rheumatoid arthritis

DOI: https://doi.org/10.1002/adma.202514070