Mitochondrial Electron Flow Dynamics Imaging for Assessing Mitochondrial Quality and Drug Screening

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Mitochondrial quality control is paramount for cellular development, with mitochondrial electron flow (Mito‐EF) playing a central role in maintaining homeostasis. However, unlike visible protein entities, which can be monitored through chemical biotechnology, regulating by invisible entities such as Mito‐EF has remained elusive. Here, tracker (Mito‐EFT) four‐pronged probe design presented to elucidate the dynamic mechanisms of Mito‐EF's involvement control. Heightened aggregation fiber‐like healthy mitochondria compared round‐like damaged demonstrated, revealed correlated morphological remodeling, particularly regions undergoing fission and fusion, show signal associated cristae maintained Dynamin‐Related Protein 1 (DRP1). This underscores importance considering assessing parameters. A novel drug screening evaluation parameter, also introduced screen discover mitochondrial‐targeted therapeutic modulators. provides new avenues investigating homeostasis control, offering potent tool screening.

Язык: Английский

---

Mdm38/LETM1 couples ion homeostasis and proteostatic mechanisms in the inner mitochondrial membrane

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

The mitochondrial inner membrane is among the most protein-dense cellular membranes. Its functional integrity maintained through a concerted action of several conserved mechanisms that are far from clear. Here, using baker's yeast model, we functionally characterize Mdm38/LETM1, disease-related protein implicated in translation and ion homeostasis, although molecular basis these connections remains elusive. Our findings reveal novel role for Mdm38 maintaining homeostasis within membrane. Specifically, demonstrate required iron signaling bioavailability mitochondria to vacuoles. These processes linked m- AAA quality control protease, whose unrestrained activity disrupts assembly stability respiratory chain complexes Mdm38-deficient cells. study highlights central biology reveals how it couples proteostatic across subcellular compartments.

Язык: Английский

---

MSCs-EVs harboring OA immune memory reprogram macrophage phenotype via modulation of the mt-ND3/NADH-CoQ axis for OA treatment

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 25, 2025

Osteoarthritis (OA) is a prevalent degenerative joint disease and current therapies are insufficient to halt its progression. Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) offer promising therapeutic potential for OA treatment, their efficacy can be enhanced through strategic engineering approaches. Inspired by the immune memory of adaptive system, we developed an engineered strategy impart OA-specific MSCs-EVs. Using Luminex technology, inflammatory factors (IFN-γ, IL-6, TNF-α), which mimic microenvironment, were identified used prime MSCs, generating memory-bearing MSCs-EVs (iEVs). Proteomic analysis complementary experiments conducted evaluate iEVs' effects on macrophage phenotypic reprogramming. iEVs, particularly IL-6-EV, exhibited potent immunoregulatory functions along with ability modulate mitochondrial metabolism. Both in vitro vivo, IL-6-EV significantly reprogrammed macrophages towards M2 subtype, effectively suppressing articular inflammation Mechanistic studies revealed that facilitated polarization regulating oxidative phosphorylation via mt-ND3/NADH-CoQ axis. This study introduces enhance MSCs-EVs' OA. Multi-omics biological validation demonstrate potential, providing new insights future application other clinical conditions.

Язык: Английский

---

Mitochondrial genetics, signalling and stress responses

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Язык: Английский

---

Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Abstract Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in‐growth resulting from structural disturbances within the (IVD) major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate immune microenvironment mitochondrial communication attenuate The antioxidant metal‐polyphenol nanoparticle system sequentially macrophage phenotype delivery efficiency. strategy circumvents necessity for isolation preservation techniques that are typically required in conventional transplantation procedures. Furthermore, it facilitates effective sustained mitochondria damaged cells. In vivo, this formulation effectively preserves IVD height, maintains integrity nucleus pulposus (NP), restores pain thresholds. Thus, nanoplatform offers an approach traditional surgical treatments significant potential clinical application.

Язык: Английский

---

A Mitochondria-targeted Fluoropolymer Nanoparticle with Inherent Mitophagy Inducing and Red Fluorescence Properties for Treatment of Atherosclerosis

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Mitophagy is crucial for the selective autophagic degradation of damaged mitochondria, helping to maintain both mitochondrial and cellular homeostasis. Here, we report a fluoroalkylated polypyridinium that specifically targets mitochondria exhibits high activity in mitophagy induction. The polymer effectively restores function alleviates inflammatory response foam cells by activating mitophagy, displays inherent red fluorescence under physiological conditions, allowing direct tracing its biodistribution in vivo. Besides, nanoparticle shows serum stability due antifouling properties fluoroalkyl tags. After intravenous administration, reduces oxidative stress, promotes decreases senescence atherosclerotic plaques, contributing therapeutic efficacy. This study presents novel effective strategy treatment atherosclerosis other dysfunction-related conditions.

Язык: Английский

---

Mitochondrial heat production: the elephant in the lab…

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

Retromer promotes the lysosomal turnover of mtDNA

Science Advances, Год журнала: 2025, Номер 11(14)

Опубликована: Апрель 4, 2025

Mitochondrial DNA (mtDNA) is exposed to multiple insults produced by normal cellular function. Upon mtDNA replication stress, the mitochondrial genome transfers endosomes for degradation. Using proximity biotinylation, we found that stress leads rewiring of proteome, increasing mitochondria’s association with lysosomal and vesicle-related proteins. Among these, retromer complex, particularly VPS35, plays a pivotal role extracting components. The promotes formation mitochondrial-derived vesicles shuttled lysosomes. mtDNA, however, directly shuttles recycling organelle in BAX-dependent manner. Moreover, using Drosophila model carrying long deletion on (ΔmtDNA), ΔmtDNA activates specific transcriptome profile counteract damage. Here, Vps35 expression restores homoplasmy alleviates associated defects. Hence, demonstrate existence previously unknown quality control mechanism matrix essential lysosomes turnover relieve

Язык: Английский

---

Effects of sodium hypochlorite on the viability and osteogenic differentiation of dental pulp stem cells in regenerative pulp therapy

Journal of Dental Sciences, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

---

Protective Effects of Mdivi‐1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

Neuroinflammation is one of the essential pathogeneses cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots evidences showed microglia presented mitochondrial fragmentation during SAE. This study investigated protective effects and novel mechanisms inhibiting via division inhibitor 1 (Mdivi-1) on in The SAE model was performed by cecal ligation puncture (CLP), Mdivi-1 administrated intraperitoneal injection. Morris water maze to assess function. Mitochondrial morphology observed electron microscope or MitoTracker staining. qRT-PCR, immunofluorescence staining, western blots were used detect inflammatory factors protein content, respectively. Flow cytometry polarization hippocampal microglia. Bioinformatics analysis verify hypotheses. administration alleviated sepsis-induced fragmentation, activation, polarization, damage. neuroinflammation oxidative stress suppressed NF-κB Keap1/Nrf2/HO-1 pathways following administration; meanwhile, pyroptosis reduced, which associated with enhanced autophagosome formation p62 elevation administration. Inhibition beneficial disturbance, are related alleviating neuroinflammation, stress, pyroptosis.

Язык: Английский

---