98%
921
2 minutes
20
Dysfunctional mitochondria are a hallmark of T cell ageing and contribute to organismal ageing. This arises from the accumulation of reactive oxygen species (ROS), impaired mitochondrial dynamics, and inefficient removal of dysfunctional mitochondria. Both cell-intrinsic and cell-extrinsic mechanisms for removing mitochondria and their byproducts have been identified in T cells. In this review, we explore how T cells manage mitochondrial damage through changes in mitochondrial metabolism, mitophagy, asymmetric mitochondrial inheritance, and mitochondrial transfer, highlighting the impact of these mechanisms on T cell ageing and overall organismal ageing. We also discuss current therapeutic strategies aimed at removing dysfunctional mitochondria and their byproducts and propose potential new therapeutic targets that may reverse immune ageing or organismal ageing.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/s44319-025-00536-z | DOI Listing |
Sci Adv
September 2025
Department of Cell & Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA-where mutant and wild-type mtDNA coexist-complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
Instituto de Biología Celular y Neurociencias "Prof. De Robertis" (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
Rationale: Autism spectrum disorders (ASD) are a group of neurodevelopmental and multifactorial conditions with cognitive manifestations. The valproic acid (VPA) rat model is a well-validated model that successfully reproduces the behavioral and neuroanatomical alterations of ASD. Previous studies found atypical brain connectivity and metabolic patterns in VPA animals: local glucose hypermetabolism in the prefrontal cortex, with no metabolic changes in the hippocampus.
View Article and Find Full Text PDFCancer Biol Med
September 2025
Yan'an Key Laboratory of Microbial Drug Innovation and Transformation, Yan'an Medical School of Yan'an University, Yan'an 716000, China.
The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction. Mitochondria exhibit characteristics, such as decreased oxidative phosphorylation efficiency, abnormal accumulation of reactive oxygen species in liver cancer and promoting tumor proliferation and drug resistance through the Warburg effect, as the core of energy metabolism and apoptosis regulation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial autophagy (mitophagy) further enhance the invasive and metastatic capabilities of liver cancer.
View Article and Find Full Text PDFTrends Biotechnol
September 2025
Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laborator
Type 2 diabetes (T2D) is characterized by persistent and unresolved tissue inflammation caused by the infiltration and dysregulation of immune cells. Current therapeutics targeting inflammatory immune cells for T2D remain limited. In this study, we analyzed single cell RNA from metabolic organs in T2D, revealing increased macrophage accumulation and a pathogenic macrophage subpopulation defined as NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammatory and metabolically activated macrophages.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Cen
Macrophages play crucial roles in the progression of liver diseases. Increasing studies have shown that mesenchymal stem cells (MSCs) and their extracellular vesicles (MSC-EVs) could reshape the liver immune microenvironment by regulating the function and phenotype of macrophages, thereby exerting a therapeutic effect on liver diseases. Mitochondria, apart from being the central hub of energy metabolism, also finely regulate macrophage-mediated innate immune responses by modulating reactive oxygen species levels, cell polarization, and cell death.
View Article and Find Full Text PDF