bims-mitrat 2025-04-20 papers

Adv Mater. 2025 Apr 14. e2500495

Artificial Mitochondrial Nanorobots Deliver Energy In Vivo by Oral Administration.

Nan Li, Min Zhou, Ziyu Wu, Yu Chen, Yu Duan, Ziqiang Zhang, Zhuolin Wu, Xue Xia, Jian Shen, Chun Mao, Mimi Wan.

Delivering energy in vivo is essential for treating mitochondrial damage-related diseases. Current methods, including natural mitochondrial transplantation and artificial energy delivery systems, lack non-destructive, external energy-free, and clinically viable potential solutions. Here, artificial mitochondrial nanorobots (AMNs) carrying high-energy phosphate bonds rebuild the in vivo energy supply system to provide energy. Using ischemic heart disease (IHD) as an energy-deficient disease model and the oral route, which has high patient compliance and facilitates long-term administration, to investigate the therapeutic efficacy of AMNs. AMNs remain stable in the gastrointestinal tract, cross the intestinal barrier via a barrier-crossing unit, and target damaged heart tissue and cardiomyocytes using a motion unit chemotactically. Intracellularly, their energy-generating unit provides high-energy phosphate bonds for ATP synthesis (duration 12 h), while synergistically reducing inflammation and restoring cell viability. At the same frequency of administration, oral AMNs (50 mg kg-1) match intravenous AMNs (10 mg kg-1) in therapeutic efficacy, offering a convenient approach to improving cardiac function. Transcriptomics confirm that 200 µg AMNs emulate 5 × 10⁶ natural mitochondria, restoring energy metabolism and structural function in damaged hearts at the genetic level. This innovative design opens a new pathway for the construction of artificial energy delivery systems in vivo.

Keywords: artificial mitochondria; energy delivery; ischemic heart disease; nanorobots; oral administration

DOI: https://doi.org/10.1002/adma.202500495

Brain Res. 2025 Apr 16. pii: S0006-8993(25)00206-9. [Epub ahead of print] 149647

Effects of mitochondrial O-GlcNAcylation in pericytes after mechanical injury.

Ji Hyun Park, Dong Bin Back, Shuzhen Guo, Masayoshi Tanaka, Hajime Takase, Michael J Whalen, Ken Arai, Kazuhide Hayakawa, Eng H Lo.

Damage to vascular cells comprise an important part of traumatic brain injury (TBI) but the underlying pathophysiology remains to be fully elucidated. Here, we investigate the loss of O-Linked β-N-acetylglucosamine(O-GlcNAc) modification (O-GlcNAcylation) and mitochondrial disruption in vascular pericytes as a candidate mechanism. In mouse models in vivo, TBI rapidly induces vascular oxidative stress and down-regulates mitochondrial O-GlcNAcylation. In pericytes but not brain endothelial cultures in vitro, mechanical stretch injury down-regulates mitochondrial O-GlcNAcylation. This is accompanied by disruptions in mitochondrial dynamics, comprising a decrease in mitochondrial fusion and an increase in mitochondrial fission proteins. Pharmacologic rescue of endogenous mitochondrial O-GlcNAcylation with an O-GlcNAcase inhibitor Thiamet-G or addition of exogenous O-GlcNAc-enhanced extracellular mitochondria ameliorates the mitochondrial disruption in pericytes damaged by mechanical injury. Finally, in a pericyte-endothelial co-culture model, mechanical injury increased trans-cellular permeability; adding Thiamet-G or O-GlcNAc-enhanced extracellular mitochondria rescued trans-cellular permeability following mechanical injury. These proof-of-concept findings suggest that mitochondrial O-GlcNAcylation in pericytes may represent a novel therapeutic target for ameliorating oxidative stress and vascular damage after mechanical injury following TBI.

Keywords: Mitochondrial dynamics; O-GlcNAcylation; Oxidative stress; Traumatic brain injury; Vascular pericyte

DOI: https://doi.org/10.1016/j.brainres.2025.149647

Stem Cell Res Ther. 2025 Apr 15. 16(1): 180

Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.

Yun Liao, Stacia Octaviani, Zhen Tian, Samuel R Wang, Chunlan Huang, Jian Huang.

Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, and long-term stability of hematopoietic stem cells (HSCs). Recent research highlights the central importance of MQC in HSC biology, particularly the roles of mitophagy, mitochondrial biogenesis, fission, fusion and mitochondrial transfer in regulating HSC function. Mitophagy ensures the removal of damaged mitochondria, maintaining low levels of reactive oxygen species (ROS) in HSCs, thereby preventing premature aging and functional decline. Concurrently, mitochondrial biogenesis adjusts key metabolic regulators such as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring the metabolic needs of HSCs are met. Additionally, mitochondrial transfer, as an essential form of intercellular material exchange, facilitates the transfer of functional mitochondria from bone marrow stromal cells to HSCs, contributing to damage repair and metabolic support. Although existing studies have revealed the significance of MQC in maintaining HSC function, the precise molecular mechanisms and interactions among different regulatory pathways remain to be fully elucidated. Furthermore, the potential role of MQC dysfunction in hematopoietic disorders, including its involvement in disease progression and therapeutic resistance, is not yet fully understood. This review discusses the molecular mechanisms of MQC in HSCs, its functions under physiological and pathological conditions, and its potential therapeutic applications. By summarizing the current progress in this field, we aim to provide insights for further research and the development of innovative treatment strategies.

Keywords: Hematopoietic stem cell; Mitochondrial biogenesis; Mitochondrial dynamics; Mitochondrial metabolism; Mitochondrial quality control; Mitochondrial transfer; Mitophagy

DOI: https://doi.org/10.1186/s13287-025-04304-7