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MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation

Authors: Mick, David U.; Dennerlein, Sven; Wiese, Heike; Reinhold, Robert; Pacheu-Grau, David; Lorenzi, Isotta; Sasarman, Florin; +4 Authors

MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation

Abstract

Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.

Keywords

Biochemistry, Genetics and Molecular Biology(all), Membrane Proteins, Membrane Transport Proteins, Mitochondrial Membrane Transport Proteins, Mitochondria, Electron Transport Complex IV, Mitochondrial Proteins, Cytosol, Protein Biosynthesis, Mitochondrial Precursor Protein Import Complex Proteins, Cyclooxygenase 1, Humans

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
210
Top 1%
Top 10%
Top 1%
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