Mitochondrial Protein Synthesis Adapts to Influx of Nuclear-Encoded Protein

Summary

Mitochondrial ribosomes translate membrane integral core subunits of the oxidative phosphorylation system encoded by mtDNA. These translation products associate with nuclear-encoded, imported proteins to form enzyme complexes that produce ATP. Here, we show that human mitochondrial ribosomes display translational plasticity to cope with the supply of imported nuclear-encoded subunits. Ribosomes expressing mitochondrial-encoded COX1 mRNA selectively engage with cytochrome c oxidase assembly factors in the inner membrane. Assembly defects of the cytochrome c oxidase arrest mitochondrial translation in a ribosome nascent chain complex with a partially membrane-inserted COX1 translation product. This complex represents a primed state of the translation product that can be retrieved for assembly. These findings establish a mammalian translational plasticity pathway in mitochondria that enables adaptation of mitochondrial protein synthesis to the influx of nuclear-encoded subunits.

Graphical Abstract

Highlights

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  Mitochondrial ribosomes display translational plasticity

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  COX1 translation in mitochondria is stalled in the absence of nuclear-encoded COX4

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  A ribosome nascent chain complex of COX1 is a primed state for complex IV assembly

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  MITRAC regulates translation via COX1 ribosome nascent chain complexes interaction

Abstract

Mitochondrial translation displays plasticity, allowing the adaptation to the availability of a nuclear-encoded complex subunit.