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MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation.

Mick, David U; Dennerlein, Sven; Wiese, Heike; Reinhold, Robert; Pacheu-Grau, David; Lorenzi, Isotta; Sasarman, Florin; Weraarpachai, Woranontee; Shoubridge, Eric A; Warscheid, Bettina; Rehling, Peter.
Cell; 151(7): 1528-41, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23260140
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.
Selo DaSilva