The Role of AAA+ Proteases in Mitochondrial Protein Biogenesis, Homeostasis and Activity Control
Mitochondria are specialised organelles that are structurally and functionally integrated into cells in the vast majority of eukaryotes. They are the site of numerous enzymatic reactions, some of which are essential for life. The double lipid membrane of
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The Role of AAA+ Proteases in Mitochondrial Protein Biogenesis, Homeostasis and Activity Control Wolfgang Voos, Linda A. Ward, and Kaye N. Truscott
Abstract Mitochondria are specialised organelles that are structurally and functionally integrated into cells in the vast majority of eukaryotes. They are the site of numerous enzymatic reactions, some of which are essential for life. The double lipid membrane of the mitochondrion, that spatially defines the organelle and is necessary for some functions, also creates a physical but semi-permeable barrier to the rest of the cell. Thus to ensure the biogenesis, regulation and maintenance of a functional population of proteins, an autonomous protein handling network within mitochondria is required. This includes resident mitochondrial protein translocation machinery, processing peptidases, molecular chaperones and proteases. This review highlights the contribution of proteases of the AAA+ superfamily to protein quality and activity control within the mitochondrion. Here they are responsible for the degradation of unfolded, unassembled and oxidatively damaged proteins as well as the activity control of some enzymes. Since most knowledge about these proteases has been gained from studies in the eukaryotic microorganism Saccharomyces cerevisiae, much of the discussion here centres on their role in this organism. However, reference is made to mitochondrial AAA+ proteases in other organisms, particularly in cases where they play a unique role such as the mitochondrial unfolded protein response. As these proteases influence mitochondrial function in both health and disease in humans, an understanding of their regulation and diverse activities is necessary.
W. Voos (*) Institut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, 53115 Bonn, Germany e-mail: [email protected] L.A. Ward • K.N. Truscott (*) Department of Biochemistry, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC 3086, Australia e-mail: [email protected] D.A. Dougan (ed.), Regulated Proteolysis in Microorganisms, Subcellular Biochemistry 66, DOI 10.1007/978-94-007-5940-4_9, © Springer Science+Business Media Dordrecht 2013
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Introduction The highly compartmentalised nature of a eukaryotic cell brings about increased complexity relative to a prokaryotic cell, with respect to the biogenesis and regulation of its proteome. With the vast majority of eukaryotic cellular proteins encoded by the nuclear genome and synthesised on cytosolic ribosomes, many steps are required for their successful trafficking from the cytosol to the correct subcellular location and their subsequent maturation and folding. Furthermore, proteins regardless of their subcellular location, need to be removed in a regulated manner to allow their replenishment or to alter their concentration in the cell. The balance between protein biogenesis and degradation determines the concentration of a particular type of protein in the cell at any particular
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