Thioredoxins (TRXs) are important proteins involved in redox regulation of metabolism. In plants, it has been shown that the mitochondrial metabolism is regulated by the mitochondrial TRX system. However, the functional significance of TRX h2, which is found at both cytosol and mitochondria, remains unclear. Arabidopsis plants lacking TRX h2 showed delayed seed germination and reduced respiration alongside impaired stomatal and mesophyll conductance, without impacting photosynthesis under ambient O2 conditions. However, an increase in the stoichiometry of photorespiratory CO2 release was found during O2‐dependent gas exchange measurements in trxh2 mutants. Metabolite profiling of trxh2 leaves revealed alterations in key metabolites of photorespiration and in several metabolites involved in respiration and amino acid metabolism. Decreased abundance of serine hydroxymethyltransferase and glycine decarboxylase (GDC) H and L subunits as well as reduced NADH/NAD+ ratios were also observed in trxh2 mutants. We further demonstrated that the redox status of GDC‐L is altered in trxh2 mutants in vivo and that recombinant TRX h2 can deactivate GDC‐L in vitro, indicating that this protein is redox regulated by the TRX system. Collectively, our results demonstrate that TRX h2 plays an important role in the redox regulation of mitochondrial photorespiratory metabolism.
Non-small cell lung cancer (NSCLC), one of the most common causes of cancer-related death, is a worldwide public health problem. MicroRNAs (miRNAs) have recently been identified as a novel class of regulators of carcinogenesis and tumor progression, including miRNAs associated with NSCLC. This study aimed to explore the role of miR-522 in NSCLC and the mechanisms underlying this role. We report here that miR-522 expression was significantly increased in both human NSCLC tissues and cell lines. Furthermore, an MTT assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay kit and flow cytometry confirmed that the inhibition of miR-522 suppressed NSCLC cells proliferation and induced apoptosis. Compared with miR-522 overexpression, miR-522 inhibitor markedly reduced cells migration and invasion, as indicated by wound-healing and transwell assays. In addition, a luciferase assay identified DENN/MADD domain containing 2D (DENND2D) as a direct target of miR-522. qRT-PCR and western blot analyses indicated the reciprocal expression of miR-522 and DENND2D in NSCLC tissue samples. DENND2D was involved in miR-522 induced proliferation and metastasis of NSCLC cells by a miRNA-masking antisense oligonucleotides (miR-mask) technology. These data highlight a novel molecular interaction between miR-522 and DENND2D, which indicates that targeting miR-522 may constitute a potential therapy for NSCLC.
Arabidopsis contains eight different h-type thioredoxins (Trx) being distributed in different cell organelles. Although Trx h2 is deemed to be confined to mitochondria, its subcellular localization and function are discussed controversially. Here, cell fractionation studies were used to clarify this question, showing Trx h2 protein to be exclusively localized in microsomes rather than mitochondria. Furthermore, Arabidopsis trxo1, trxh2 and trxo1h2 mutants were analyzed to compare the role of Trx h2 with mitochondrial Trx o1. Under medium light, trxo1 and trxo1h2 showed impaired growth, while trxh2 was similar to wild type. In line with this, trxo1 and trxo1h2 clustered differently from wild type with respect to nocturnal metabolite profiles, revealing a decrease in ascorbate and glutathione redox states. Under fluctuating light, these genotypic differences were attenuated. Instead, the trxo1h2 double mutant showed an improved NADPH redox balance, compared to wild type, accompanied by increased photosynthetic efficiency, specifically in the high-light phases. Conclusively, Trx h2 and Trx o1 are differentially localized in microsomes and mitochondria, respectively, which is associated with different redox-active functions and effects on plant growth in constant light, while there is a joint role of both Trxs in regulating NADPH redox balance and photosynthetic performance in fluctuating light.
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