MIRO-1 interacts with VDAC-1 to regulate mitochondrial membrane potential in Caenorhabditis elegans.

Precise regulation of mitochondrial fusion and fission is essential for cellular activity and animal development. Imbalances between these processes can lead to fragmentation and loss of normal membrane potential in individual mitochondria. In this study, we show that MIRO-1 is stochastically elevated in individual fragmented mitochondria and is required for maintaining mitochondrial membrane potential. We further observe a higher level of membrane potential in fragmented mitochondria in fzo-1 mutants and wounded animals. Moreover, MIRO-1 interacts with VDAC-1, a crucial mitochondrial ion channel located in the outer mitochondrial membrane, and this interaction depends on the residues E473 of MIRO-1 and K163 of VDAC-1. The E473G point mutation disrupts their interaction, resulting in a reduction of the mitochondrial membrane potential. Our findings suggest that MIRO-1 regulates membrane potential and maintains mitochondrial activity and animal health by interacting with VDAC-1. This study provides insight into the mechanisms underlying the stochastic maintenance of membrane potential in fragmented mitochondria.

Redox-sensitive CDC-42 clustering promotes wound closure in C. elegans.

Tissue damage induces immediate-early signals, activating Rho small GTPases to trigger actin polymerization essential for later wound repair. However, how tissue damage is sensed to activate Rho small GTPases locally remains elusive. Here, we found that wounding the C. elegans epidermis induces rapid relocalization of CDC-42 into plasma membrane-associated clusters, which subsequently recruits WASP/WSP-1 to trigger actin polymerization to close the wound. In addition, wounding induces a local transient increase and subsequent reduction of H2O2, which negatively regulates the clustering of CDC-42 and wound closure. CDC-42 CAAX motif-mediated prenylation and polybasic region-mediated cation-phospholipid interaction are both required for its clustering. Cysteine residues participate in intermolecular disulfide bonds to reduce membrane association and are required for negative regulation of CDC-42 clustering by H2O2. Collectively, our findings suggest that H2O2-regulated fine-tuning of CDC-42 localization can create a distinct biomolecular cluster that facilitates rapid epithelial wound repair after injury.

Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling.

Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair.

MiR-532 downregulation of the Wnt/ß-catenin signaling via targeting Bcl-9 and induced human intervertebral disc nucleus pulposus cells apoptosis.

OBJECTIVE: Intervertebral disc degeneration was characterized with aberrant intervertebral disc nucleus pulposus cells apoptosis. MiR-532 was reported to be up-regulated in the patients with intervertebral disc degeneration. However, the role of miR-532 in intervertebral disc degeneration remains unclear. Thus, current study aim to investigate the effects of miR-532 on human intervertebral disc nucleus pulposus cells. METHODS: Quantitative PCR was firstly used to evaluate the level of miR-532 expression in intervertebral disc nucleus pulposus cells. Then, luciferase reporter assays was used to confirm the target genes of miR-532. The effects of miR-532 on cell proliferation were assayed using EdU transfection. Next, apoptosis level was examined by flow cytometry utilizing Annexin V-FITC/PI double staining, and the protein expression in cells was detected with Western blotting. Finally, The expression of ß-catenin protein was demonstrated by fluorescence confocal microscopy and the interaction between ß-catenin and Bcl-9 was detected by co-immunoprecipitation. RESULTS: MiR-532 was significantly upregulated in patient with intervertebral disc degeneration. In addition, intervertebral disc nucleus pulposus cells apoptosis was significantly increased in miR-532 mimics treated group. Moreover, Bcl-9 was confirmed to be a direct target of miR-532 via luciferase reporter assays and western blot assays. CONCLUSION: MiR-532 downregulation of the Wnt/ß-catenin signaling via targeting Bcl-9 and induced human intervertebral disc nucleus pulposus cells apoptosis.

Nanoporous gold supported cobalt oxide microelectrodes as high-performance electrochemical biosensors.

Tremendous demands for electrochemical biosensors with high sensitivity and reliability, fast response and excellent selectivity have stimulated intensive research on developing versatile materials with ultrahigh electrocatalytic activity. Here we report flexible and self-supported microelectrodes with a seamless solid/nanoporous gold/cobalt oxide hybrid structure for electrochemical nonenzymatic glucose biosensors. As a result of synergistic electrocatalytic activity of the gold skeleton and cobalt oxide nanoparticles towards glucose oxidation, amperometric glucose biosensors based on the hybrid microelectrodes exhibit multi-linear detection ranges with ultrahigh sensitivities at a low potential of 0.26 V (versus Ag/AgCl). The sensitivity up to 12.5 mA mM⁻¹ cm⁻² with a short response time of less than 1 s gives rise to ultralow detection limit of 5 nM. The outstanding performance originates from a novel nanoarchitecture in which the cobalt oxide nanoparticles are incorporated into pore channels of the seamless solid/nanoporous Au microwires, providing excellent electronic/ionic conductivity and mass transport for the enhanced electrocatalysis.

[The effect of aerobic exercise on serum IL-4 and TNF-alpha of patients with allergic rhinitis].

OBJECTIVE: To investigate the effect of aerobic exercise on immune factor IL-4, TNF-alpha in patients with allergic rhinitis, which provide a theoretical basis for the treatment of allergic rhinitis. METHOD: Thirty-two allergic rhinitis patients were selected and divided into a control group (14 people) and the experimental group (18 people). During the treatment, both groups receive conventional symptomatic treatment. Meanwhile, aerobic exercise therapy is applied to the experimental group for 40 - 60 minutes a day, 3 - 4 days a week. Serum IL-4, TNF-alpha and allergic rhinitis symptoms graded scoring were tested before and after 6 month therapy. RESULT: After six months of exercise intervention, the 11-4, and TNF-alpha levels of experimental group were significantly lower than the level of control group. The symptoms score is also significantly decreased in experimental group. CONCLUSION: Aerobic exercise had good therapeutic effect in patients with allergic rhinitis. The mechanism may be that aerobic exercise can reduce the level of IL-4 and TNF-alpha, which can relieve infiltration and activation of inflammatory cells.