Abstract
Mitochondrial precursor proteins are synthesized in the cytosol and subsequently imported into mitochondria. The import of mitochondrial intermembrane space proteins is coupled with their oxidative folding and governed by the mitochondrial intermembrane space import and assembly (MIA) pathway. The cytosolic steps that precede mitochondrial import are not well understood. We identified a role for the ubiquitin-proteasome system in the biogenesis of intermembrane space proteins. Interestingly, the function of the ubiquitin-proteasome system is not restricted to conditions of mitochondrial protein import failure. The ubiquitin-proteasome system persistently removes a fraction of intermembrane space proteins under physiological conditions, acting as a negative regulator in the biogenesis of this class of proteins. Thus, the ubiquitin-proteasome system plays an important role in determining the levels of proteins targeted to the intermembrane space of mitochondria.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Copper Transport Proteins
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Cytosol / metabolism
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Intracellular Membranes / metabolism*
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Leupeptins / pharmacology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism*
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Mitochondrial Precursor Protein Import Complex Proteins
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Mutation
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Ubiquitin / metabolism*
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Ubiquitinated Proteins / metabolism
Substances
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COX17 protein, S cerevisiae
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Cation Transport Proteins
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Copper Transport Proteins
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Leupeptins
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MIA40 protein, S cerevisiae
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Membrane Proteins
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Membrane Transport Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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Molecular Chaperones
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Multienzyme Complexes
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Pet191 protein, S cerevisiae
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RPN13 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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TIM10 protein, S cerevisiae
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TIM13 protein, S cerevisiae
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Tim8 protein, S cerevisiae
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Tim9 protein, S cerevisiae
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Ubiquitin
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Ubiquitinated Proteins
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PRE1 protein, S cerevisiae
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PRE2 protein, S cerevisiae
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Proteasome Endopeptidase Complex
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde