CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response

Mitochondrial dysfunction is becoming one of the main pathology factors involved in the etiology of neurological disorders. Recently, mutations of the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) which encode two homologous proteins that belong to the mitochondrial CHCH domain protein family, are linked to Parkinson’s disease and amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), respectively. However, the physiological and pathological roles of these twin proteins have not been well elaborated. Here, we show that, in physiological conditions, CHCHD2 and CHCHD10 interact with OMA1 and suppress its enzyme activity, which not only restrains the initiation of the mitochondrial integrated response stress (mtISR), but also suppresses the processing of OPA1 for mitochondrial fusion. Further, during mitochondria stress-induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment, CHCHD2 and CHCHD10 translocate to the cytosol and interacte with eIF2a, which attenuates mtISR overactivation by suppressing eIF2a phosphorylation and its downstream response. As such, knockdown of CHCHD2 and CHCHD10 triggers mitochondrial ISR, and such cellular response is enhanced by CCCP treatment. Therefore, our findings demonstrate the first “mtISR suppressor” localized in mitochondria for regulating stress responses in mammalian cells, which has a profound pathological impact on the CHCH2/CHCH10-linked neurodegenerative disorder.Subject terms: Stress signalling, Mitochondria     

Improving aquaporin Z expression in <Emphasis Type="Italic">Escherichia coli</Emphasis> by fusion partners and subsequent condition optimization

Aquaporin Z (AqpZ), a typical orthodox aquaporin with six transmembrane domains, was expressed as a fusion protein with TrxA in E. coli in our previous work. In the present study, three fusion partners (DsbA, GST and MBP) were employed to improve the expression level of this channel protein in E. coli. The result showed that, compared with the expression level of TrxA-AqpZ, five- to 40-fold increase in the productivity of AqpZ with fusion proteins was achieved by employing these different fusion partners, and MBP was the most efficient fusion partner to increase the expression level. By using E. coli C43 (DE3)/pMAL-AqpZ, the effects of different expression conditions were investigated systematically to improve the expression level of MBP-AqpZ in E. coli. The high productivity of MBP-AqpZ (200 mg/l) was achieved under optimized conditions. The present work provides a novel approach to improve the expression level of membrane proteins in E. coli.     

Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis

Bioassay-guided fractionation of the chloroform-soluble fraction of Morus bombycis, using an in vitro PTP1B inhibitory assay led to the identification of three 2-arylbenzofurans, albafuran A (1), mulberrofuran W (2) and mulberrofuran D (6), along with three chalcone-derived Diels–Alder products, kuwanon J (3), kuwanon R (4), and kuwanon V (5). Compounds 1–6 showed remarkable inhibitory activity against PTP1B with IC₅₀ values ranging from 2.7 to 13.8 μM. Inhibition kinetics were analyzed by Lineweaver–Burk plots, which suggested that compounds 1–6 inhibited PTP1B in a mixed-type manner. The present results indicate that the respective lipophilic and hydroxyl groups of 2-arylbenzofurans and chalcone-derived Diels–Alder products play an important role in inhibition of PTP1B.     

季节、环境温度与黄鼠冬眠的关系

观察了达乌尔黄鼠在实验室内冬眠的一般情况。常温黄鼠的体温有着规律性的年周期,与环境温度的年周期变动不完全呈依从关系。出眠初期(4月下旬),动物体温高而稳定。4月至6月常温黄鼠的平均体温(皮温)为35.6℃,波动菹围32—37.5℃。随着体重达到顶峰,体温逐渐降低。8月份部分黄鼠出现低于32℃的低常体温,表明部分黄鼠自8月盛夏开始冬眠。但就整个种群而言,北京地区实验室内黄鼠冬眠季自9月下半月开始。3月底止,共6.5个月。秋季室温下降,动物入眠趋势增长。浅低体温(31.9—15℃)的比数逐渐升高。9月至12月,低体温(低于31.9℃)的百分比从47％增至84.8％,反映了动物从浅冬眠向深冬眠过渡。1月至2月份,低体温占85％以上,深低体温(低于15℃)占绝对优势。标志着动物种群的深眠月份。秋季动物从常温期向冬眠期转化的界线是不清的,而春季从冬眠期向常温相转化的界限却比较明显。     

Molecular characterization of flavonol synthase from poplar and its application to the synthesis of 3-<Emphasis Type="Italic">O</Emphasis>-methylkaempferol

Biosynthesis of flavonoid derivatives requires enzyme(s) having high reactivity as well as regioselectivity. We have synthesized 3-O-kaempferol from naringenin using two enzymes. The first reaction, in which naringenin is converted to kaempferol, is mediated by flavonol synthase (FLS). An FLS (PFLS) with strong catalytic activity was cloned and characterized from the genome sequence of the poplar (Populus deltoides). PFLS consists of a 1,008 bp ORF encoding a 38 kDa protein. PFLS was expressed in Escherichia coli with a glutathione-S-transferase (GST) tagging. The purified recombinant PFLS was characterized. Catalytically, it was more efficient than the previously characterized FLSs. A mixture of two E. coli transformants harboring either PFLS or ROMT9 (a kaempferol 3-O-methyltransferase) converted naringenin into 3-O-methylkaempferol.     

An Ultralong Lifespan and Low‐Temperature Workable Sodium‐Ion Full Battery for Stationary Energy Storage

Presently, commercialization of sodium‐ion batteries (SIBs) is still hindered by the relatively poor energy‐storage performance. In addition, low‐temperature (low‐T) Na storage is another principal concern for the wide application of SIBs. Unfortunately, the Na‐transfer kinetics is extremely sluggish at low‐T, as a result, there are few reports on low‐T SIBs. Here, an advanced low‐T sodium‐ion full battery (SIFB) assembled by an anode of 3D Se/graphene composite and a high‐voltage cathode (Na₃V₂(PO₄)₂O₂F) is developed, exhibiting ultralong lifespan (over even 15 000 cycles, the capacity retention is still up to 86.3% at 1 A g^?1), outstanding low‐T energy storage performance (e.g., all values of capacity retention are >75% after 1000 cycles at temperatures from 25 to ?25 °C at 0.4 A g^?1), and high‐energy/power properties. Such ultralong lifespan signifies that the developed sodium‐ion full battery can be used for longer than 60 years, if batteries charge/discharge once a day and 80% capacity retention is the standard of battery life. As a result, the present study not only promotes the practicability and commercialization of SIBs but also points out the new developing directions of next‐generation energy storage for wider range applications.     

Lack of association between AQP4 polymorphisms and risk of inflammatory demyelinating disease in a Korean population

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating autoimmune inflammatory diseases that affect the central nervous system (CNS). Previous genome-wide or candidate gene studies have suggested that genetic variants might be associated with the risk of MS or NMO. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the CNS, and its expression is decreased in NMO lesions due to astrocyte cytotoxicity. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with MS and/or NMO. However, there have been few replication studies in various ethnic populations. This study, as the first of its kind performed in an Asian population, investigated associations of AQP4 SNPs with the risk of inflammatory demyelinating disease (IDD), including MS and NMO, in a Korean population. A total of seven common AQP4 SNPs were selected based on status of linkage disequilibrium (LD), and then genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of IDD, including MS and NMO (P > 0.05). Further replications in larger cohorts and other ethnic groups are needed.