Biogenesis of mitochondrial porin: The import pathway

Summary We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble signal sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance.     

Phytanic acid: production from phytol, its breakdown and role in human disease

Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease, belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human disease and the way it is produced from phytol. Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006     

Importance of NPA motifs in the expression and function of water channel aquaporin-1

The asparagine-proline-alanine sequences (NPA motifs) are highly conserved in aquaporin water channel family. Crystallographic studies of AQP1 structure demonstrated that the two NPA motifs are in the narrow central constriction of the channel, serving to bind water molecules for selective and effi-cient water passage. To investigate the importance of the two NPA motifs in the structure, function and biogenesis of aquaporin water channels, we generated AQP1 mutations with NPA1 deletion, NPA2 de-letion and NPA1,2 double deletion. The coding sequences of the three mutated cDNAs were subcloned into the mammalian expression vector pcDNA3.1 to form expression plasmids. We established stably transfected CHO cell lines expressing these AQP1 mutants. Immunofluorescence indicated that all the three mutated AQP1 proteins are expressed normally on the plasma membrane of stably transfected CHO cells, suggesting that deletion of NPA motifs does not influence the expression and intracellular processing of AQP1. Functional analysis demonstrated that NPA1 or NPA2 deletion reduced AQP1 water permeability by 49.6% and 46.7%, respectively, while NPA1,2 double deletion had little effect on AQP1 water permeability. These results provide evidence that NPA motifs are important for water per-meation but not essential for the expression, intracellular processing and the basic structure of AQP1 water channel.     

Marine indoles of novel substitution pattern from the acorn wormGlossobalanus sp.

Summary 4,6-Dibromoindole and 4,6-dibromo-2-methylindole have been isolated from the acorn wormGlossobalanus sp. The biosynthetic implications of this finding are discussed.We wish to thank Prof. Paul J. Scheuer, University of Hawaii for his encouragement and for use of his facilities during spectroscopic work. T.H. gratefully acknowledges the giving of a travel grant by the University of the Ryukyus Foundation for International Exchange.     

In vitro systems in the study of peroxisomal protein import

Our level of understanding of peroxisome biogenesis in comparison with other cellular organelles is rudimentary, yet the fragments of information available indicate that the targeting and import of peroxisomal proteins occur by fundamentally different mechanisms. Genetic studies have identified a number of genes required for peroxisome assembly, but in most cases the functions of the gene products remain unknown. In vitro protein translocation systems have played a prominent role in unravelling the biochemistry of protein translocation into other organelles. This review considers some of the requirements for establishing a bona fide peroxisomal import assay and discusses the findings which have emerged as a result of using such experimental systems.     

Effects of Chlorophyll Availability on Fluorescence Components of Photosystems in the ORF469-Deletion Mutant of Cyanobacterium

ＩｎｔｒｏｄｕｃｔｉｏｎＩｎｃｙａｎｏｂａｃｔｅｒｉａ ,ｔｗｏ ｐａｔｈｗａｙｓｏｆ ｐｒｏｔｏ ｃｈｌｏｒｏｐｈｙｌｌｉｄｅ (Ｐｃｈｌｉｄｅ)ｒｅｄｕｃｔｉｏｎａｎｄｃｈｌｏｒｏｐｈｙｌｌ(Ｃｈｌ)ｂｉｏｓｙｎｔｈｅｓｉｓａｐｐｅａｒｔｏｅｘｉｓｔ:ｏｎｅｉｓｌｉｇｈｔ ｄｅｐｅｎｄｅｎｔ ,ｔｈｅｏｔｈｅｒｉｓｌｉｇｈｔ ｉｎｄｅｐｅｎｄｅｎｔ[1,2 ] .Ａｔｌｅａｓｔｔｈｒｅｅ ｐｏｌｙｐｅｐｔｉｄｅｓａｒｅｉｎｖｏｌｖｅｄｉｎｔｈｅｌｉｇｈｔ ｉｎｄｅｐｅｎｄｅｎｔｐａｔｈｗａｙ .Ｏｎｅｏｆｔｈｅｓｅｐ…     

Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells

Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells. Received 10 March 2006; received after revision 28 April 2006; accepted 30 May 2006     

Human Genome and Diseases:¶Cellular and molecular aspects of Zellweger syndrome and other peroxisome biogenesis disorders

Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous metabolic processes, both catabolic and anabolic, including β-oxidation of very long chain fatty acids, metabolism of hydrogen peroxide, plasmalogen biosynthesis and bile acid synthesis. In several genetic diseases, there is either isolated deficiency of a specific peroxisomal protein (single-protein deficiencies) or a defect in the formation of the organelle with loss of multiple peroxisomal functions (peroxisome biogenesis disorders). X-linked adrenoleukodystrophy is an example of the former, and the Zellweger spectrum of the latter. Peroxisome biogenesis disorders are inherited in an autosomal recessive manner and result from mutations in any of at least 12 PEX genes that encode peroxins. This article reviews the peroxisomal system, the clinical, biochemical and molecular aspects of peroxisomal disorders, and discusses recent scientific advances in the understanding of peroxisome biogenesis. Received 16 October 2001; received after revision 2 January 2002; accepted 3 January 2002     

Molecular biology of chloroplast biogenesis: gene expression, protein import and intraorganellar sorting

The chloroplast is the hallmark organelle of plants. It performs photosynthesis and is therefore required for photoautotrophic plant growth. The chloroplast is the most prominent member of a family of related organelles termed plastids which are ubiquitous in plant cells. Biogenesis of the chloroplast from undifferentiated proplastids is induced by light. The generally accepted endosymbiont hypothesis states that chloroplasts have arisen from an internalized cyanobacterial ancestor. Although chloroplasts have maintained remnants of the ancestral genome (plastome), the vast majority of the genes encoding chloroplast proteins have been transferred to the nucleus. This poses two major challenges to the plant cell during chloroplast biogenesis: First, light and developmental signals must be interpreted to coordinately express genetic information contained in two distinct compartments. This is to ensure supply and stoichiometry of abundant chloroplast components. Second, developing chloroplasts must efficiently import nuclear encoded and cytosolically synthesized proteins. A subset of proteins, including such encoded by the plastome, must further be sorted to the thylakoid compartments for assembly into the photosynthetic apparatus. Received 1 September 2000; received after revision 27 October 2000; accepted 1 November 2000     

PGC-1 α 与运动能力

长期的耐力训练可诱导成年的骨骼肌发生一系列的生理性适应,其中包括快肌纤维向慢肌纤维转换,线粒体的生物合成等。过氧化物酶体增殖物受体γ共激活因子1α(PGC-1a)可能在运动诱导骨骼肌的适应机制起着重要作用:增强骨骼肌氧化代谢能力,从而增强利用脂肪和碳水化合物的能力。但研究发现PGC-1a基因敲除小鼠进行长期的训练仍能够诱导线粒体蛋白表达增加。长期耐力训练可诱导骨骼肌PGC-1a表达增加和激活确切生理作用仍需要进一步研究。