过氧化物酶体与病原真菌的致病性

过氧化物酶体(Peroxisome)是一类单层膜的细胞器,普遍存在于各种真核细胞中。过氧化物酶体是丰富的酶库,含有至少50种酶类,参与生物体的多种生理代谢过程,如乙醛酸循环、脂肪酸的β-氧化及活性氧的调节等。近年来,日益增多的研究表明过氧化物酶体和病原真菌的乙醛酸循环及脂肪酸的β-氧化功能的发挥密切相关,并影响病原真菌的致病性。总结过氧化物酶体中酶的种类和功能,评述过氧化物酶体与乙醛酸循环、脂肪酸β-氧化和病原真菌致病性的关系。     

过氧化物酶体生物发生研究进展

过氧化物酶体是存在于真核细胞中的一种亚细胞器,主要功能是参与脂肪酸等脂质的代谢过程和氧化应激的调节。近年来研究发现,多种疾病都与过氧化物酶体的生物发生异常有关。过氧化物酶体的生物发生指过氧化物酶体的形成过程,包括从头合成和分裂增殖两条途径。两条途径中,参与过氧化物酶体生物发生的蛋白质,即peroxin(PEX)的基因发生突变,会导致过氧化物酶体生成障碍,引起疾病的发生。因此,就过氧化物酶体生物发生的研究进展进行综述,有助于为相关疾病的诊断和治疗提供参考和依据。     

过氧化物酶体的稳态维持机制与膜接触位点

过氧化物酶体是保守存在于真核生物中的一种细胞器,参与多种生化代谢过程,包括脂肪酸β氧化反应、活性氧的产生和降解等。过氧化物酶体在生物发生和应对环境胁迫过程中,通过数量和时空分布的规律性动态变化,实现质量控制,以维持其生化代谢的稳态,从而保持机体的正常生命活动。同时,作为真核细胞的代谢枢纽,过氧化物酶体功能的正常发挥与稳态维持需要与其他细胞器相互协作。过氧化物酶体膜接触位点在过氧化物酶体与各细胞器相互连接和交流中发挥着重要作用。近年来,过氧化物酶体稳态维持机制和膜接触位点的组成和功能成为国内外相关研究的热点,本文对相关研究的进展进行了综述。     

过氧化物酶体降解与疾病

过氧化物酶体是细胞中一种参与脂肪酸代谢、缩醛磷脂合成和氧化应激等功能的细胞器,其数量会根据细胞和细胞所处微环境的不同而发生变化,这种变化又与过氧化物酶体本身的降解密切相关.虽然一直以来,过氧化物酶体都被线粒体的光芒所掩盖,但是近年来,随着过氧化物酶体研究的逐渐增多,人们对于过氧化物酶体的降解也有了更全面的了解.本文主要...     

酵母过氧化物酶体的形成机制

过氧化物酶体是细胞中一种重要的细胞器.过氧化物酶体在细胞功能的发挥和人体健康方面有着重要作用.目前,以酵母过氧化物酶体为模型,研究过氧化物酶体的形成机制是研究热点.从过氧化物酶体起源、生成方式介绍最新研究进展,总结在酵母细胞中参与过氧化物酶体形成的必需基因(pex),及其编码Peroxin蛋白在过氧化物酶体形成过程中的...     

过氧化物酶体的生物发生与疾病

过氧化物酶体的膜蛋白和酶分子由核基因编码,在游离的核糖体上合成之后,由定位信号引导靶向运输并组装到过氧化物酶体的。本文就过氧化物酶体膜蛋白信号ｍＰＴＳ、酶分子信号ＰＴＳ１Ｔ ＰＴＳ２、酶分子运进过氧化物酶体的模型以及由于过氧化物酶体生物发生的障碍而引起的疾病加以讨论。     

PEX基因在过氧化物酶体形成及真菌致病性中的作用

过氧化物酶体(peroxisomes)是一类真核生物中普遍存在的细胞器,参与β-氧化、乙醛酸循环等多种重要的生化代谢。研究表明,过氧化物酶体在植物病原真菌侵染寄主过程中具有着举足轻重的作用。参与过氧化物酶体形成与增殖的基因,通常称为PEX基因。近年来,越来越多的PEX基因在植物病原真菌中得到鉴定,真菌过氧化物酶体的形成机制及其在植物病原真菌生长发育和致病过程中的作用越来越受到研究者的关注。本文围绕PEX 基因在过氧化物酶体形成中的作用、对过氧化物酶体相关生化代谢的影响,以及与植物病原真菌生长发育和致病性的关系进行了综述,以期为植物病原真菌致病机理研究和病害防控提供借鉴和参考。     

植物过氧化物酶体在活性氧信号网络中的作用

过氧化物酶体是高度动态、代谢活跃的细胞器,主要参与脂肪酸等脂质的代谢及产生和清除不同的活性氧(reactive oxygen species, ROS)。ROS是细胞有氧代谢的副产物。当胁迫长期作用于植物,过量的ROS会引起氧胁迫,损害细胞结构和功能的完整性,导致细胞代谢减缓,活性降低,甚至死亡;但低浓度的ROS则作为分子信号,感应细胞ROS/氧化还原变化,从而触发由环境因素导致的过氧化物酶体动力学以及依赖ROS信号网络改变而产生快速、特异性的应答。ROS也可以通过直接或间接调节细胞生长来控制植物的发育,是植物发育的重要调节剂。此外,过氧化物酶体的动态平衡由ROS、过氧化物酶体蛋白酶及自噬过程调节,对于维持细胞的氧化还原平衡至关重要。本文就过氧化物酶体中ROS的产生和抗氧化剂的调控机制进行综述,以期为过氧化物酶体如何感知环境变化,以及在细胞应答中,ROS作为重要信号分子的研究提供参考。     

过氧化物酶体功能异常与阿尔茨海默病

过氧化物酶体是一种广泛存在于真核细胞内的异质性细胞器,具有多种酶活性,主要功能是参与脂肪酸氧化、磷脂合成和氧化应激平衡的调节等过程。研究发现,过氧化物酶体功能异常引起的脑组织中极长链脂肪酸聚集、植烷酸贮积、二十二碳六烯酸(docosahexaenoic acid,DHA)和缩醛磷脂减少等与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展密切相关。尽管具体的机制尚不清楚,但目前认为,过氧化物酶体功能异常很可能是AD发生发展的始动因素之一。因此,就过氧化物酶体功能异常与AD之间关系的研究进展进行综述,有助于为AD的发病机制研究提供线索和依据。     

植物过氧化物酶体在活性氧信号网络中的作用北大核心CSCD

过氧化物酶体是高度动态、代谢活跃的细胞器,主要参与脂肪酸等脂质的代谢及产生和清除不同的活性氧(reactive oxygen species,ROS)。ROS是细胞有氧代谢的副产物。当胁迫长期作用于植物,过量的ROS会引起氧胁迫,损害细胞结构和功能的完整性,导致细胞代谢减缓,活性降低,甚至死亡;但低浓度的ROS则作为分子信号,感应细胞ROS/氧化还原变化,从而触发由环境因素导致的过氧化物酶体动力学以及依赖ROS信号网络改变而产生快速、特异性的应答。ROS也可以通过直接或间接调节细胞生长来控制植物的发育,是植物发育的重要调节剂。此外,过氧化物酶体的动态平衡由ROS、过氧化物酶体蛋白酶及自噬过程调节,对于维持细胞的氧化还原平衡至关重要。本文就过氧化物酶体中ROS的产生和抗氧化剂的调控机制进行综述,以期为过氧化物酶体如何感知环境变化,以及在细胞应答中,ROS作为重要信号分子的研究提供参考。     

真菌非编码RNA

非编码RNAs(non-coding RNA,ncRNAs)是一类在生物体中广泛存在的且不编码蛋白质的功能性RNA分子,直接在RNA水平发挥作用,影响生物体的生命活动.动植物ncRNAs的研究已有大量的文献报道,而真菌ncRNAs的研究报道则相对较少.近年来,随着研究技术的进步,人们在真菌中也发现了不少种类的ncRNAs,如snoRNA派生的ncRNAs、长片段ncRNAs (long non-coding RNAs,lncRNAs)、干扰小RNA(smallinterfering RNAs,siRNAs)、Killer双链RNA病毒,及丝状真菌的新型ncRNAs等.这些ncRNAs在真菌中具有多种多样的生物学功能,涉及基因的转录翻译、RNA加工修饰、染色体结构稳定性,以及真菌致病性等.因此,研究真菌ncRNAs不仅能为了解真菌的基因表达调控系统和生长提供重要信息,也能为阐明致病性真菌的致病机理提供新思路,对真菌性疾病的治疗具有重大意义.本文对真菌ncRNAs的发现、起源、分类、生物学功能等进行了综述,以期为进一步深入研究真菌ncRNAs提供一定的理论与研究基础.     

The peroxisome RING-finger complex is required for meiocyte formation in the fungus Podospora anserina

Peroxisomes are involved in a variety of metabolic pathways and developmental processes. In the filamentous fungus Podospora anserina, absence of different peroxins implicated in peroxisome matrix protein import leads to different developmental defects. Lack of the RING-finger complex peroxin PEX2 blocks sexual development at the dikaryotic stage, while in absence of both receptors, PEX5 and PEX7, karyogamy and meiosis can proceed and sexual spores are formed. This suggests a complex role for PEX2 that prompted us to study the developmental involvement of the RING-finger complex. We show that, like PEX2, the two other proteins of the complex, PEX10 and PEX12, are equally implicated in peroxisome biogenesis and that absence of each or all these proteins lead to the same developmental defect. Moreover, we demonstrate that peroxisome localization of PEX2 is not drastically affected in the absence of PEX10 and PEX12 and that the upregulation of these latter RING-finger peroxins does not compensate for the lack of a second one, suggesting that the three proteins work together in development but independent of their function in peroxisome biogenesis.     

Isolation and characterization of novel phenotype CHO cell mutants defective in peroxisome assembly, using ICR191 as a potent mutagenic agent

To elucidate molecular and cellular mechanisms of peroxisome biogenesis, we have isolated Chinese hamster ovary (CHO) cell mutants defective in peroxisome biogenesis by making use of enhanced green fluorescent protein (EGFP) and a frameshift-inducing mutagen ICR191. CHO-TKa cells stably expressing Pex2p were transformed with a cDNA encoding EGFP fused with peroxisomal targeting signal type 2 (PTS2-EGFP), termed Tka/EG2. TKa/EG2 cells were mutagenized with ICR191 and cultured in the presence of P9OH (9-(1'-pyrene) nonanol) followed by an exposure to UV. P9OH/UV-resistant and morphologically peroxisome-deficient mutant cells were isolated by directly observing cytosolic localization of EGFP, without cell staining. By a combination of cell-fusion and PEX transfection, we determined complementation groups (CGs) of 16 cell mutants isolated here. The mutants were classified into five CGs, including pex2, pex3, pex5, pex6, and pex7 cell mutants. In contrast to typical pex6 mutants with the impaired import of both PTS1- and PTS2-proteins, two clones, ZPEG236 and ZPEG244, showed a distinct, novel phenotype where PTS1-protein import was normal despite the abrogated PTS2 import. Dysfunction of Pex3p in pex3 ZPEG 238 was due to one base (G) insertion in the codon for Asn7 resulting in a frameshift, thereby inducing a distinct 31 amino-acid sequence and a termination. pex2 ZPEG239 showed a mutation in codon GAG for Glu(201) to a nonsense mutation, TAG. Thus, the method developed here using ICR191 could be useful for isolation of further novel cell mutants impaired in peroxisome biogenesis.     

Inhibitors of COPI and COPII do not block PEX3-mediated peroxisome synthesis

In humans, defects in peroxisome biogenesis are the cause of lethal diseases typified by Zellweger syndrome. Here, we show that inactivating mutations in human PEX3 cause Zellweger syndrome, abrogate peroxisome membrane synthesis, and result in reduced abundance of peroxisomal membrane proteins (PMPs) and/or mislocalization of PMPs to the mitochondria. Previous studies have suggested that PEX3 may traffic through the ER en route to the peroxisome, that the COPI inhibitor, brefeldin A, leads to accumulation of PEX3 in the ER, and that PEX3 overexpression alters the morphology of the ER. However, we were unable to detect PEX3 in the ER at early times after expression. Furthermore, we find that inhibition of COPI function by brefeldin A has no effect on trafficking of PEX3 to peroxisomes and does not inhibit PEX3-mediated peroxisome biogenesis. We also find that inhibition of COPII-dependent membrane traffic by a dominant negative SAR1 mutant fails to block PEX3 transport to peroxisomes and PEX3-mediated peroxisome synthesis. Based on these results, we propose that PEX3 targeting to peroxisomes and PEX3-mediated peroxisome membrane synthesis may occur independently of COPI- and COPII-dependent membrane traffic.     

PEX11 promotes peroxisome division independently of peroxisome metabolism

The PEX11 peroxisomal membrane proteins are the only factors known to promote peroxisome division in multiple species. It has been proposed that PEX11 proteins have a direct role in peroxisomal fatty acid oxidation, and that they only affect peroxisome abundance indirectly. Here we show that PEX11 proteins are unique in their ability to promote peroxisome division, and that PEX11 overexpression promotes peroxisome division in the absence of peroxisomal metabolic activity. We also observed that mouse cells lacking PEX11beta display reduced peroxisome abundance, even in the absence of peroxisomal metabolic substrates, and that PEX11beta(-/-) mice are partially deficient in two distinct peroxisomal metabolic pathways, ether lipid synthesis and very long chain fatty acid oxidation. Based on these and other observations, we propose that PEX11 proteins act directly in peroxisome division, and that their loss has indirect effects on peroxisome metabolism.     

一株产黑色素的地丝霉新种

从贵州大学真菌资源研究所一4℃冰箱中分离到一株能产生黑色素的地丝霉G014512菌株,经产孢结构、菌落特征及5.8S-ITS序列研究分析,鉴定为地丝霉属Geomyces的一个新种,贵阳地丝霉Geomyces guiyangensis。该菌株能在0℃生长,最适生长温度范围在15–25℃,生长上限温度为40℃。微生物产生黑色素的应用研究越来越受关注,贵阳地丝霉具有潜在的应用价值。     

Newly identified Chinese hamster ovary cell mutants defective in peroxisome assembly represent complementation group A of human peroxisome biogenesis disorders and one novel group in mammals

We isolated peroxisome biogenesis-defective mutants from rat PEX2-transformed Chinese hamster ovary (CHO) cells, using the 9-(1'-pyrene)nonanol/ultraviolet method. A total of 18 mutant cell clones showing cytosolic localization of catalase were isolated. By complementation group (CG) analysis by means of PEX cDNA transfection and cell fusion, cell mutants, ZP124 and ZP126, were found to belong to two novel CGs of CHO mutants. Mutants, ZP135 and ZP167, were also classified to the same CG as ZP124. Further cell fusion analysis using 12 CGs fibroblasts from patients with peroxisome deficiency disorders such as Zellweger syndrome revealed that ZP124 belonged to human CG-A, the same group as CG-VIII in the United States. ZP126 could not be classified to any of human and CHO CGs. These mutants also showed typical peroxisome assembly-defective phenotypes such as severe loss of catalase latency and impaired biogenesis of peroxisomal enzymes. Collectively, ZP124 represents CG-A, and ZP126 is in a newly identified CG distinct from the 14 mammalian CGs previously characterized.     

海洋曲霉来源的新天然产物

海洋真菌由于其遗传背景复杂、代谢产物种类多且产量高,已成为海洋微生物新天然产物的主要来源,从我们对2010–2013年初的海洋微生物来源新天然产物的统计来看,研究最多的是曲霉属(Aspergillus)真菌,占海洋真菌来源新天然产物的31%。本文从菌株来源、化合物结构及其生物活性等方面,综述了自1992年第一个海洋曲霉天然产物到2014年8月已报道的共512个海洋曲霉来源的新天然产物。这些海洋天然产物具有丰富的化学多样性,且36%的化合物表现出细胞毒、抑菌、抗氧化和抗寄生虫等生物活性;含氮化合物是其主要的结构类型、约占曲霉源海洋天然产物总数的52%,也是出现活性化合物比例最高的结构类型、约40%的含氮化合物具有生物活性,其中脱氢二酮哌嗪生物碱halimide的化学衍生物plinabulin已结束II期临床研究,并于2015年第三季度开始在美国和中国进行III期临床研究,用于治疗转移性的晚期非小细胞肺癌。