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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,wereport a comprehensive dissection
of early cytochromec 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.
