Molecular mechanisms and physiological functions of mitophagy

Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.     

Plant TGNs: dynamics and physiological functions

In all eukaryotic cells, a membrane trafficking system connects the post-Golgi organelles, including the trans-Golgi network (TGN), endosomes, and vacuoles. This complex network plays critical roles in several higher-order functions in multicellular organisms. The TGN, one of the important organelles for protein transport in the post-Golgi network, functions as a sorting station, where cargo proteins are directed to the appropriate post-Golgi compartments. The TGN has been considered to be a compartment belonging to the Golgi apparatus, located on the trans side of the Golgi apparatus. However, in plant cells, recent studies have suggested that the TGN is an independent, dynamic organelle that possesses features different than those of TGNs in animal and yeast cells. In this review, we summarize recent progress regarding the dynamics and physiological functions of the plant TGN.     

The physiological functions of prion protein

Foreign DNA can be readily integrated into the genomes of mammalian embryonic cells by retroviral infection, DNA microinjection, and transfection protocols. However, the transgenic DNA is frequently not expressed or is expressed at levels far below expectation. In a number of organisms such as yeast, plants, Drosophila, and nematodes, silencing of transfected genes is triggered by the interaction between adjacent or dispersed copies of genes of identical sequence. We set out to determine whether a mechanism similar to repeat-induced gene silencing (RIGS) is responsible for the silencing of transgenes in murine embryonal carcinoma stem cells. We compared the expression of identical reporter gene constructs in cells carrying single or multiple copies and found that the level of expression per integrated copy was more than 10-fold higher in single-copy integrants. In cells carrying tandem copies of the transgene, many copies were methylated and clones frequently failed to express both copies of near-identical integrated alleles. Addition of extra copies of the reporter gene coding sequence reduced the level of expression from the same reporter driven by a eukaryotic promoter. We also found that inhibitors of histone deacetylase such as trichostatin A forestall the silencing of multicopy transgenes, suggesting that chromatin mediates the silencing of transfected genes. This evidence is consistent with the idea that RIGS does occur in mammalian embryonic stem cells although silencing of single-copy transgenes also occurs, suggesting that RIGS is only one of the mechanisms responsible for triggering transgene silencing.     

Chaperones in regulation and restoration of physiological functions

Protective effects of the HSP70 expression in heat stress, sleep deprivation, epilepsy, enhanced anxiety, psycho-emotional stress, physical loads, are described, and data on the HSP70 effects upon characteristics of sleep and somatic-visceral functions in homeothermic animals are cited. Prospects of using the HSP70 "inductors" are discussed as well as the HSP70 preparations use in therapy of large range of pathological conditions.     

Mitochondrial division: molecular machinery and physiological functions

Mitochondrial division has emerged as a key mechanism for this essential organelle to maintain its structural integrity, intracellular distribution, and functional competence. An evolutionarily conserved dynamin-related GTPase, Dnm1p/Drp1, interacts with other proteins to form the core machinery involved in mitochondrial division. We summarize recent progress in understanding how the division machinery assembles onto mitochondria and how mitochondrial division contributes to cellular physiology and human diseases.     

Obestatin: its physicochemical characteristics and physiological functions

Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene with ghrelin, was initially reported to reduce food intake, body weight gain, gastric emptying and suppress intestinal motility through an interaction with the orphan receptor GPR39. However, recently reports have shown that above findings had been questioned by several groups. Further studies explained that obestatin was involved in inhibiting thirst and anxiety, improving memory, regulating sleep, affecting cell proliferation, and increasing the secretion of pancreatic juice enzymes. We also identified that obestatin could stimulate piglet liver and adipose cell proliferation, and inhibit the secretion of IGF-I. According to the controversy over the effects and the cognate ligand of obestatin, here we provide the latest review on the structure, distribution and physiological functions of obestatin.     

Difructose anhydrides: their mass-production and physiological functions

Difructose anhydrides (DFAs) are the smallest cyclic disaccharides consisting of two fructose residues, and are expected to have novel physiological functions from their unique structures and properties. For mass-production of alpha-D-fructofuranose-beta-D-fructofuranose-2',1:2,3'-dianhydride (DFA III) and beta-D-fructofuranose-beta-D-fructofuranose-2',6:2,6'-dianhydride (DFA IV), Arthrobacter sp. H65-7 and A. nicotinovorans GS-9 were selected as the best producers of inulase II, which produced DFA III from inulin and LFTase, which produced DFA IV from levan. The enzymes were purified and their genes were subsequently cloned and expressed in E. coli at higher levels than in the original bacteria. Thus, it became possible to provide a large amount of DFA III and DFA IV for evaluating their physiological properties. DFA III and DFA IV have half the sweetness of sucrose, but cannot be digested by the digestive system of rats. Their use by the intestinal microorganisms was observed in vivo even though their assimilation could not be detected in vitro. This implied that they were degraded by an unknown system in the intestine. It was also found that they affected calcium absorption mainly in the small intestine through mechanisms different from the known stimulants such as fructooligosaccharides and raffinose.     

Molecular mechanism and physiological functions of clathrin-mediated endocytosis

Clathrin-mediated endocytosis is the endocytic portal into cells through which cargo is packaged into vesicles with the aid of a clathrin coat. It is fundamental to neurotransmission, signal transduction and the regulation of many plasma membrane activities and is thus essential to higher eukaryotic life. Morphological stages of vesicle formation are mirrored by progression through various protein modules (complexes). The process involves the formation of a putative FCH domain only (FCHO) initiation complex, which matures through adaptor protein 2 (AP2)-dependent cargo selection, and subsequent coat building, dynamin-mediated scission and finally auxilin- and heat shock cognate 70 (HSC70)-dependent uncoating. Some modules can be used in other pathways, and additions or substitutions confer cell specificity and adaptability.     

钙网蛋白的生理及病理生理学作用

钙网蛋白（calreticulin,CRT）是内质网／肌浆网主要的Ca2^＋结合蛋白,通过协助蛋白质正确折叠和维持细胞Ca^2＋稳态而参与调节细胞凋亡、黏附、类固醇敏感性基因表达和自身免疫反应等,并与多种人类疾病的发生、发展和预后相关。本文综述钙网蛋白的生理功能及其在心肌肥大与衰竭、血管新生和应激等病理状态下的变化。     

Characteristics and physiological functions of polyphenols from apples

Apples contain many kinds of polyphenols, and the main components are oligomeric procyanidins. Applephenon is apple polyphenol extract produced commercially from unripe apples, and has been used as food additive in order to prevent oxidation of components in foods and its application in functional foods is expected. In a lipid metabolism regulation study, administration of Applephenon has the potential to exert strong anti-oxidative activity and to inhibit consumption of vitamin E and anti-oxidative enzymes. Double blind clinical trials of Applephenon on pediatric patients with atopic dermatitis, and tests using type I allergic model mice suggested that Applephenon might regulate allergic reactions. We found the no observed adverse effect level (NOAEL) of Applephenon is greater than 2000 mg/kg in a 90~day consecutive oral administration toxicity test in rats, and Applephenon is safe and acceptable based on mutagenicity tests.     

线粒体囊泡调控机制与生理功能研究进展

线粒体在细胞的生命活动过程中承担重要作用,线粒体通过自身质量控制维持线粒体健康.线粒体囊泡作为一种新型的线粒体质量控制机制,通过靶向到不同的细胞器,调控线粒体内氧化/受损蛋白的降解;激活免疫系统,发挥抗原呈递和杀灭细菌的功能,从而维持线粒体以及细胞的稳态平衡.本文就线粒体囊泡的调控机制以及生物学功能的研究进展进行综述.     

Evolutionary-biological peculiarities of transglutaminase. Structure,physiological functions,application

Transglutaminase (TG; protein-glutamine γ-glutamyltransferase, EC 2.3.2.13) catalyzes the acyl transfer reactions that introduce the covalent ɛ-(γ-glutamyl)lysine bonds between proteins to form polymers of high mol. mass. Properties of the TG enzyme are described. Its structure is considered, there are described items of the TG life cycle and stability, its biological (physiological) role, and significance in pathology and medicine as well as obtaining the purified enzyme preparations and their use. TGs from different sources—of animal and microbial origin—are compared. Mechanism of catalysis of microbial TG is discussed. Characteristics of isoenzymes from different biological sources are presented.