Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway.

The ring finger protein 113A (RNF113A) serves as an E3 ubiquitin ligase and a subunit of the spliceosome. Mutations in the RNF113A gene are associated with X-linked trichothiodystrophy (TTD). However, the cellular roles of RNF113A remain largely unknown. In this study, we performed transcriptome profiling of RNF113A knockout (KO) HeLa cells using RNA sequencing and revealed the upregulation of NRF2 pathway-associated genes. Further analysis confirmed that the KO of RNF113A promotes nuclear localization of the NRF2 protein and elevates the mRNA levels of NRF2 target genes. RNF113A KO cells showed high levels of intracellular reactive oxygen species (ROS) and decreased resistance to cell death following H2O2 treatment. Additionally, RNF113A KO cells more sensitively formed stress granules (SGs) under arsenite-induced oxidative stress. Moreover, RNF113A KO cells exhibited a decrease in glutathione levels, which could be attributed to a reduction in GLUT1 expression levels, leading to decreased glucose uptake reactions and lower intracellular glucose levels. These alterations potentially caused a reduction in ROS scavenging activity. Taken together, our findings suggest that the loss of RNF113A promotes oxidative stress-mediated activation of the NRF2 pathway, providing novel insights into RNF113A-associated human diseases.

Potential range shift of a long-distance migratory rice pest, Nilaparvata lugens, under climate change.

The biogeographical range shift of insect pests is primarily governed by temperature. However, the range shift of seasonal long-distance migratory insects may be very different from that of sedentary insects. Nilaparvata lugens (BPH), a serious rice pest, can only overwinter in tropical-to-subtropical regions, and some populations migrate seasonally to temperate zones with the aid of low-level jet stream air currents. This study utilized the CLIMEX model to project the overwintering area under the climate change scenarios of RCP2.6 and RCP8.5, both in 2030s and 2080s. The overwintering boundary is predicted to expand poleward and new overwintering areas are predicted in the mid-latitude regions of central-to-eastern China and mid-to-southern Australia. With climate change, the habitable areas remained similar, but suitability decreased substantially, especially in the near-equatorial regions, owing to increasing heat stress. The range shift is similar between RCP2.6-2030s, RCP2.6-2080s, and RCP8.5-2030s, but extreme changes are projected under RCP8.5-2080s with marginal areas increasing from 27.2 to 38.8% and very favorable areas dropping from 27.5 to 3.6% compared to the current climate. These findings indicate that climate change will drive range shifts in BPH and alter regional risks differently. Therefore, international monitoring programs are needed to effectively manage these emerging challenges.

Modulating intestinal health: Impact of chitooligosaccharide molecular weight on suppressing RAGE expression and inflammatory response in methylglyoxal-induced advanced glycation end-products.

The accumulation of methylglyoxal (MGO) produced in high-temperature processed foods and excessive production in the body contributes to intestinal barrier dysfunction. In this study, we investigated the effects of chitooligosaccharides (COSs) of different molecular weights (<1 kDa, 1-3 kDa, 3-5 kDa, 5-10 kDa, and >10 kDa) on MGO-induced intestinal barrier dysfunction. We investigated the effect of COSs on inhibiting intracellular MGO accumulation/MGO-derived AGEs production and regulating the receptor for AGE (RAGE)-mediated downstream protein expression, including proteins related to apoptosis and inflammation, intestinal barrier integrity, and paracellular permeability. Pretreatment with COSs ameliorated MGO-induced increased RAGE protein expression, activation of apoptotic cascade/inflammatory response, loss of intestinal epithelial barrier integrity, and increased paracellular permeability, ameliorating intestinal dysfunction through MGO scavenging. 1-3 kDa COSs most effectively ameliorated MGO-induced intestinal dysfunction. Our results suggest the potential of COSs in improving intestinal health by ameliorating intestinal barrier dysfunction by acting as an MGO scavenger and highlighting the need for the optimization of the molecular weight of COSs to optimize its protective effects.

Absence of Slc39a14/Zip14 in mouse pancreatic beta cells results in hyperinsulinemia.

Zinc is an essential component of the insulin protein complex synthesized in ß cells. The intracellular compartmentalization and distribution of zinc are controlled by 24 transmembrane zinc transporters belonging to the ZnT or Zrt/Irt-like protein (ZIP) family. Downregulation of SLC39A14/ZIP14 has been reported in pancreatic islets of patients with type 2 diabetes (T2D) as well as mouse models of high-fat diet (HFD)- or db/db-induced obesity. Our previous studies observed mild hyperinsulinemia in mice with whole body knockout of Slc39a14 (Zip14 KO). Based on our current secondary data analysis from an integrative single-cell RNA-seq dataset of human whole pancreatic tissue, SLC39A14 (coding ZIP14) is the only other zinc transporter expressed abundantly in human ß cells besides well-known zinc transporter SLC30A8 (coding ZnT8). In the present work, using pancreatic ß cell-specific knockout of Slc39a14 (ß-Zip14 KO), we investigated the role of SLC39A14/ZIP14-mediated intracellular zinc trafficking in glucose-stimulated insulin secretion and subsequent metabolic responses. Glucose-stimulated insulin secretion, zinc concentrations, and cellular localization of ZIP14 were assessed using in vivo, ex vivo, and in vitro assays using ß-Zip14 KO, isolated islets, and murine cell line MIN6. Metabolic evaluations were done on both chow- and HFD-fed mice using time-domain nuclear magnetic resonance and a comprehensive laboratory animal monitoring system. ZIP14 localizes on the endoplasmic reticulum regulating intracellular zinc trafficking in ß cells and serves as a negative regulator of glucose-stimulated insulin secretion. Deletion of Zip14 resulted in greater glucose-stimulated insulin secretion, increased energy expenditure, and shifted energy metabolism toward fatty acid utilization. HFD caused ß-Zip14 KO mice to develop greater islet hyperplasia, compensatory hyperinsulinemia, and mild insulin resistance and hyperglycemia. This study provided new insights into the contribution of metal transporter ZIP14-mediated intracellular zinc trafficking in glucose-stimulated insulin secretion and subsequent metabolic responses.NEW & NOTEWORTHY Metal transporter SLC39A14/ZIP14 is downregulated in pancreatic islets of patients with T2D and mouse models of HFD- or db/db-induced obesity. However, the function of ZIP14-mediated intracellular zinc trafficking in ß cells is unknown. Our analyses revealed that SLC39A14 is the only Zn transporter expressed abundantly in human ß cells besides SLC30A8. Within the ß cells, ZIP14 is localized on the endoplasmic reticulum and serves as a negative regulator of insulin secretion, providing a potential therapeutic target for T2D.

Suppression of Pro-Inflammatory M1 Polarization of LPS-Stimulated RAW 264.7 Macrophage Cells by Fucoxanthin-Rich Sargassum hemiphyllum.

Macrophages play an important role in managing the onset and progression of chronic inflammatory diseases. The primary objective of this study is to explore the antioxidant potential and anti-inflammatory properties of Sargassum hemiphyllum ethanol extract (SHE) and its fraction. SHE and its five constituent fractions were assessed for overall antioxidant capabilities and inhibitory effects on LPS-induced inflammation by modulating macrophages polarization in both RAW 264.7 macrophages and bone-marrow-derived macrophages (BMDM). Among the organic solvent fractions of SHE, the ethyl acetate fraction displayed the highest total phenolic content and total antioxidant capacity. Notably, the n-hexane (Hex) fraction showed the most substantial suppression of LPS-induced tumor necrosis factor α secretion in BMDM among the five fractions of SHE. The SHE and Hex fraction significantly reduced the heightened expression of pro-inflammatory cytokines and inflammation-inducible enzymes induced by LPS in RAW 264.7 macrophages. In particular, the SHE and Hex fraction inhibited M1 macrophage polarization by reducing the mRNA expression of M1 macrophage markers in macrophages that were polarized toward the M1 phenotype. Furthermore, the SHE and Hex fraction attenuated the induction in nuclear factor E2-related factor 2 and its target genes, which was accompanied by an alteration in antioxidant gene expression in M1-polarized BMDM. The findings suggest that both SHE and its Hex fraction exhibit inhibitory effects on LPS-triggered inflammation and oxidative stress by modulating the polarization of M1 macrophages within macrophage populations.

Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism.

Metal transporter SLC39A14/ZIP14 is localized on the basolateral side of the intestine, functioning to transport metals from blood to intestine epithelial cells. Deletion of Slc39a14/Zip14 causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose. Importantly, antibiotic treatment reverses the adipocyte phenotype of Slc39a14/Zip14 knockout (KO), suggesting a potential gut microbial role in the metabolic alterations in the Slc39a14/Zip14 KO mice. Here, we investigated the hypothesis that increased intestinal permeability and subsequent metabolic alterations in the absence of Zip14 could be in part due to alterations in gut microbial composition. Dietary metals have been shown to be involved in the regulation of gut microbial diversity and composition. However, studies linking the action of intestinal metal transporters to gut microbial regulation are lacking. We showed the influence of deletion of metal transporter Slc39a14/Zip14 on gut microbiome composition and how ZIP14-linked changes to gut microbiome community composition are correlated with changes in host metabolism. Deletion of Slc39a14/Zip14 generated Zn-deficient epithelial cells and luminal content in the entire intestinal tract, a shift in gut microbial composition that partially overlapped with changes previously associated with obesity and inflammatory bowel disease (IBD), increased the fungi/bacteria ratio in the gut microbiome, altered the host metabolome, and shifted host energy metabolism toward glucose utilization. Collectively, our data suggest a potential predisease microbial susceptibility state dependent on host gene Slc39a14/Zip14 that contributes to intestinal permeability, a common trait of IBD, and metabolic disorders such as obesity and type 2 diabetes.NEW & NOTEWORTHY Metal dyshomeostasis, intestinal permeability, and gut dysbiosis are emerging signatures of chronic disorders, including inflammatory bowel diseases, type-2 diabetes, and obesity. Studies in reciprocal regulations between host intestinal metal transporters genes and gut microbiome are scarce. Our research revealed a potential predisease microbial susceptibility state dependent on the host metal transporter gene, Slc39a14/Zip14, that contributes to intestinal permeability providing new insight into understanding host metal transporter gene-microbiome interactions in developing chronic disease.

Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.

Species-specific environmental DNA analysis of the index species in soil ecosystem, Allonychiurus kimi (Collembola: Onychiuridae).

Collembola are abundant and have significant roles in the soil ecosystem. Therefore, the phenotypic endpoints of Collembola population or community have been used as an effective bioindicator for assessing soil quality. Since the identification and counting the collembolans in the soil is a laborious and costly procedure, environmental DNA (eDNA)-based biomonitoring was proposed as an analysis tool of collembolan species found in the soil. In this study, standard primer sets for the species-specific eDNA analysis using Allonychiurus kimi, a soil bioindicator species was selected. Then, the primers were tested for specificity and sensitivity from the soil samples. Two different eDNA samples were tested: (1) eDNA samples were extracted from the soil with A. kimi individuals (intra-organismal eDNA). (2) The samples from the soil without A. kimi individuals (extra-organismal eDNA). The two primers were confirmed in their sensitivity and specificity to the two types of eDNA samples selected. C t-values from both intra- and extra-organismal eDNA showed the significant correlations to the number of inoculated A. kimi (adj. R 2 = 0.7453-0.9489). These results suggest that in excretion, egg, and other exuviae had a significant effect on eDNA analysis from soil samples taken. Furthermore, our results suggest that environmental factors should be considered when analyzing eDNA collected from soil.

Neural circuit-specific gene manipulation in mouse brain in vivo using split-intein-mediated split-Cre system.

Neural network studies require efficient genetic tools to analyze individual neural circuit functions in vivo. Thus, we developed an advanced circuit-selective gene manipulating tool utilizing anterograde and retrograde adeno-associated viruses (AAVs) encoding split-intein-mediated split-Cre. This strategy can be applied to visualize a specific neural circuit as well as manipulate multiple genes in the circuit neurons. Here, we describe the production and purification of the AAVs, viral injection to the mouse brain, and imaging analysis for a specific neural circuit. For complete details on the use and execution of this protocol, please refer to Kim et al. (2022).

3,5-Dicaffeoylquinic acid attenuates microglial activation-mediated inflammatory pain by enhancing autophagy through the suppression of MCP3/JAK2/STAT3 signaling.

Microglial activation in the spinal cord contributes to the development of inflammatory pain. Monocyte chemotactic protein 3 (MCP3) can induce microglial activation, resulting in increased pain sensitivity; however, the underlying mechanism remains poorly understood. 3,5-dicaffeoylquinic acid (3,5-DCQA) has shown protective effects against inflammation-related diseases, but the effect of 3,5-DCQA on microglial activation and inflammatory pain is not evaluated. This study aimed to investigate the effects of 3,5-DCQA on microglial activation-induced inflammatory pain. Furthermore, the underlying mechanism inhibited by 3,5-DCQA via MCP3 suppression was studied. To induce microglial activation, LPS was treated in BV2 microglial cells. The LPS-induced microglial activation and pro-inflammatory cytokines production were significantly reduced by 3,5-DCQA treatment in BV2 cells. Moreover, 3,5-DCQA suppressed LPS-induced MCP3 expression, resulting in reduced phosphorylation of JAK2/STAT3. Interestingly, the suppressed JAK2/STAT3 signaling enhanced autophagy induction in BV2 cells. The increased autophagy by 3,5-DCQA and knockout of MCP3 inhibited LPS-induced inflammatory response in BV2 cells. To establish the inflammatory pain, CFA was injected into the right paw of mice. The CFA-induced pain hypersensitivity and foot swelling were attenuated by the oral administration of 3,5-DCQA. Moreover, CFA-induced microglial activation was reduced and the autophagy markers were recovered in the spinal cord of 3,5-DCQA-administered mice. Similar results were observed in cultured primary microglia. Our findings indicate that 3,5-DCQA attenuates inflammation-mediated pain hypersensitivity by enhancing autophagy through inhibition of MCP3-induced JAK2/STAT3 signaling. Therefore, 3,5-DCQA could be a potential therapeutic agent for alleviating inflammatory pain.

Simultaneous analysis of social behaviors and neural responses in mice using round social arena system.

Stable and accurate capturing of detailed social behaviors is essential for studying rodent sociability. Here, we introduce a round social arena (RSA) system that enables close-up monitoring of detailed social behaviors in mice. We describe the steps to build RSA apparatus and set up the wiring for video synchronization. We then detail how to conduct RSA experiment with simultaneous Ca2+ imaging or optogenetics. This protocol also includes a custom MATLAB script for aligning the behavioral dataset to Ca2+ trace data. For complete details on the use and execution of this protocol, please refer to Kim et al. (2022).

Umbilicaria esculenta Extract Exhibits Antiwrinkle Activity by Suppressing ErbB2 Phosphorylation.

Umbilicaria esculenta (UE), an edible lichen, is widespread in northeast Asian countries, including China, Japan, and Korea. In the present study, we examined the antiwrinkle activity of UE. We observed that the UE extract (UEE) suppressed ultraviolet (UV)-induced matrix metalloprotein-1 (MMP-1) expression and reactive oxygen species (ROS) generation in a human keratinocyte cell line (HaCaT) and human skin tissue. In addition, UEE reversed the UV-induced decrease in collagen in the human skin tissue. Excessive and chronic UV exposure is a key factor underlying skin wrinkle formation via MMP-1 expression. As treatment with UEE disrupted the UV-activated mitogen-activated protein kinase (MAPK) signaling pathway, we applied an antibody array to unveil the underlying mechanism of UEE. Interestingly, UEE treatment inhibited ErbB2 phosphorylation, but not epidermal growth factor receptor phosphorylation, a heterodimerization partner with ErbB2. Furthermore, UEE treatment enhanced UV-suppressed phosphatase activity via ROS suppression. Collectively, our findings indicate that UEE enhances ErbB2 dephosphorylation to suppress UV-induced MMP-1 expression.

Neural circuit pathology driven by Shank3 mutation disrupts social behaviors.

Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic neural-network mechanisms underlying social dysfunction are largely unknown. Here, we demonstrate that circuit-selective mutation (ctMUT) of ASD-risk Shank3 gene within a unidirectional projection from the prefrontal cortex to the basolateral amygdala alters spine morphology and excitatory-inhibitory balance of the circuit. Shank3 ctMUT mice show reduced sociability as well as elevated neural activity and its amplitude variability, which is consistent with the neuroimaging results from human ASD patients. Moreover, the circuit hyper-activity disrupts the temporal correlation of socially tuned neurons to the events of social interactions. Finally, optogenetic circuit activation in wild-type mice partially recapitulates the reduced sociability of Shank3 ctMUT mice, while circuit inhibition in Shank3 ctMUT mice partially rescues social behavior. Collectively, these results highlight a circuit-level pathogenic mechanism of Shank3 mutation that drives social dysfunction.

By-product of Korean liquor fermented by Saccharomyces cerevisiae exhibits skin whitening activity.

Herein, the skin whitening effect of the fermentation residue of Saccharomyces cerevisiae was investigated. The fermentation residue showed radical scavenging activity and attenuated tyrosinase activity. Furthermore, the fermentation residue of S. cerevisiae significantly suppressed melanin generation in B16F10 cells. Interestingly, the sample-containing formulation exhibited increased skin whitening activity compared with that by the control formulation in a clinical study. Notably, the endogenous tyrosinase expression was not altered by the fermentation residue of S. cerevisiae; however, the enzymatic activity of tyrosinase was inhibited. Furthermore, the sample did not change TRP1 and TRP2 expression in B16F10 cells. Thus, the fermentation residue of S. cerevisiae was assumed to directly suppress the tyrosinase enzyme. It was confirmed that the fermentation residue of S. cerevisiae was a competitive inhibitor of tyrosinase. Taken together, the fermentation residue of S. cerevisiae could be a novel skin whitening agent originating from the traditional Korean liquor production process. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01062-7.

Evaluation of the combined effect of elevated temperature and cadmium toxicity on Daphnia magna using a simplified DEBtox model.

Thermal discharge and heatwaves under climate change may increase water temperature. In this study, the individual and combined effect of elevated temperature and cadmium (Cd) toxicity on somatic growth and reproduction of Daphnia magna was evaluated using a simplified dynamic energy budget model (DEBtox). The model predicted that the maximum body length (Lm) would be shorter (3.705 mm) at an elevated temperature of 25 °C than at 20 °C (3.974 mm), whereas the maximum reproduction rate (R˙m) would be higher at 25 °C (5.735) than at 20 °C (5.591). The somatic growth and reproduction of D. magna were significantly (p < 0.05) reduced with increasing Cd concentrations, and the reduction was greater at 25 than at 20 °C. Potentiation of Cd toxicity by elevated temperature was correctly simulated by assuming four toxicological modes of action influencing assimilation, somatic maintenance and growth, and reproduction. Overall, the population growth rate of D. magna was expected to decrease linearly with increasing Cd concentrations, and the decrease was expected to be higher at 25 than at 20 °C. These findings suggest a significant ecological risk of toxic metals at elevated temperature, with a mechanistic interpretation of the potentiation effect using a DEBtox modeling approach.

Multigeneration toxicity of Geunsami® (a glyphosate-based herbicide) to Allonychiurus kimi (Lee) (Collembola) from sub-individual to population levels.

Glyphosate-based herbicide (GBH) is the most widely used herbicide worldwide and has long been considered to have significantly low toxicity to non-target soil invertebrates based on short-term toxicity tests (<56 d). However, long-term GBH toxicity assessment is necessary as GBH is repeatedly applied in the same field annually because of the advent of glyphosate-resistant crops. In this study, a multigeneration test was conducted where Allonychiurus kimi (Collembola) was exposed to GBH for three generations (referred to as F0, F1, and F2) to evaluate the long-term toxic effect. The endpoints used were adult survival and juvenile production for the individual level toxicity assessment. Phospholipid profile and population age structure were the endpoints used for sub-individual and population levels, respectively. GBH was observed to have no negative effects on adult survivals of all generations, but juvenile production was found to decrease in a concentration-dependent manner, with EC50s being estimated as 572.5, 274.8, and 59.8 mg a.i. kg-1 in the F0, F1, and F2 generations, respectively. The age structure of A. kimi population produced in the test of all generations was altered by GBH exposure, mainly because of the decrease in the number of young juveniles. Further, differences between the phospholipid profiles of the control and GBH treatments became apparent over generations, with PA 16:0, PA 12:0, and PS 42:0 lipids not being detected at the highest concentration of 741 mg kg-1 in F2. Considering all our findings from sub-individual to population levels, repeated and long-term use of GBH could have significantly higher negative impacts on non-target soil organisms than expected.

Temperature and Aging Affect Glyphosate Toxicity and Fatty Acid Composition in Allonychiurus kimi (Lee) (Collembola).

Glyphosate is the most used herbicide worldwide, but enormous use of glyphosate has raised concerned about its environmental loadings. Although glyphosate is considered non-toxic, toxicity data for soil non-target organisms according to temperature and aging are scarce. This study examined the toxicity of glyphosate with the temperature (20 °C and 25 °C) and aging times (0 day and 7 days) in soil using a collembolan species, Allonychiurus kimi (Lee). The degradation of glyphosate was investigated. Fatty acid composition of A. kimi was also investigated. The half-life of glyphosate was 2.38 days at 20 °C and 1.69 days at 25 °C. At 20 °C with 0 day of aging, the EC50 was estimated to be 93.5 mg kg-1. However, as the temperature and aging time increased, the glyphosate degradation increased, so no significant toxicity was observed on juvenile production. The proportions of the arachidonic acid and stearic acid decreased and increased with the glyphosate treatment, respectively, even at 37.1 mg kg-1, at which no significant effects on juvenile production were observed. Our results showed that the changes in the glyphosate toxicity with temperature and aging time were mostly dependent on the soil residual concentration. Furthermore, the changes in the fatty acid compositions suggest that glyphosate could have a chronic effect on soil organisms.

The complete mitochondrial genome of Yuukianura szeptyckii Deharveng & Weiner 1984 (Collembola: Neanuridae).

The complete mitochondrial genome of Yuukianura szeptyckii Deharveng & Weiner 1984 was sequenced, assembled, and annotated. The mitochondrial genome of Y. szeptyckii has a length of 15,771 bp and contains 13 protein-coding genes (PCGs), 22 transfer (tRNA) genes, and 2 ribosomal RNA (rRNA) genes. Y. szeptyckii was closely clustered with the following species of Neanuridae: Bilobella aurantiaca and Friesea grisea.

The thermogenic characteristics of adipocytes are dependent on the regulation of iron homeostasis.

The development of thermogenic adipocytes concurs with mitochondrial biogenesis, an iron-dependent pathway. Iron regulatory proteins (IRP) 1 and 2 are RNA-binding proteins that regulate intracellular iron homeostasis. IRPs bind to the iron-response element (IRE) of their target mRNAs, balancing iron uptake and deposition at the posttranscriptional levels. However, IRP/IRE-dependent iron regulation in adipocytes is largely unknown. We hypothesized that iron demands are higher in brown/beige adipocytes than white adipocytes to maintain the thermogenic mitochondrial capacity. To test this hypothesis, we investigated the IRP/IRE regulatory system in different depots of adipose tissue. Our results revealed that 1) IRP/IRE interaction was increased in proportional to the thermogenic function of the adipose depot, 2) adipose iron content was increased in adipose tissue browning upon ß3-adrenoceptor stimulation, while decreased in thermoneutral conditions, and 3) modulation of iron content was linked with mitochondrial biogenesis. Moreover, the iron requirement was higher in HIB1B brown adipocytes than 3T3-L1 white adipocytes during differentiation. The reduction of the labile iron pool (LIP) suppressed the differentiation of brown/beige adipocytes and mitochondrial biogenesis. Using the 59Fe-Tf, we also demonstrated that thermogenic stimuli triggered cell-autonomous iron uptake and mitochondrial compartmentalization as well as enhanced mitochondrial respiration. Collectively, our work demonstrated that IRP/IRE signaling and subsequent adaptation in iron metabolism are a critical determinant for the thermogenic function of adipocytes.

The complete mitochondrial genome of Allonychiurus kimi (Lee, 1973) (Collembola: Onychiuridae).

The complete mitochondrial genome of Allonychiurus kimi (Lee, 1973) was sequenced, assembled, and annotated. The mitochondrial genome of A. kimi is 14,386 bp in length and contains 13 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes. A. kimi was closely clustered with the following species of the family Onychiuridae: Onychiurus orientalis, Orthonychiurus forlsomi, and Tetrodontophora bielanensis.