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Báo cáo khoa hoc : Fumarase: a paradigm of dual targeting and dual localized functions

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The enzyme fumarase is a conserved protein in all organisms with regard to its sequence, structure and function. This enzyme participates in the tri-carboxylic acid cycle in mitochondria which is essential for cellular respira-tion in eukaryotes. | IFEBS Journal MINIREVIEW Fumarase a paradigm of dual targeting and dual localized functions Ohad Yogev Adi Naamati and Ophry Pines Department of Microbiology and Molecular Genetics IMRIC Faculty of Medicine Hebrew University Jerusalem Israel Keywords bimodaltargeting dual targeting echoforms echoproteins fumarase fumarate hydratase mitochondria Correspondence O. Pines Department of Microbiology and Molecular Genetics IMRIC Faculty of Medicine Hebrew University Jerusalem 91120 Israel Fax 972 26757260 Tel 972 26757203 E-mail ophryp@ekmd.huji.ac.il These authors contributed equally to this work Received 18 May 2011 revised 31 August 2011 accepted 14 September 2011 doi 10.1111 j.1742-4658.2011.08359.x The enzyme fumarase is a conserved protein in all organisms with regard to its sequence structure and function. This enzyme participates in the tricarboxylic acid cycle in mitochondria which is essential for cellular respiration in eukaryotes. However a common theme conserved from yeast to humans is the existence of a cytosolic form of fumarase hence this protein is dual localized. We have coined identical or nearly identical proteins situated in different subcellular locations echoforms or echoproteins . Fumarase was the first example of a dual localized protein whose mechanism of distribution was found to be based on a single translation product. Consequently fumarase has become a paradigm for three unique eukaryotic cellular phenomena related to protein dual localization a distribution between mitochondria and the cytoplasm involves reverse translocation b targeting to mitochondria involves translation coupled import and c there are two echoforms possessing distinct functions in the respective sub-cellular compartments. Here we describe and discuss these fumarase related phenomena and in addition point out approaches for studying dual function of distributed proteins in particular compartment-specific depletion. In the case of fumarase the cytoplasmic function was only

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