Review
Cytosolic Events in the Biogenesis of Mitochondrial Proteins

https://doi.org/10.1016/j.tibs.2020.04.001Get rights and content
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Highlights

  • Mitochondrial proteins synthetized in the cytosol can be targeted to mitochondria at different stages of gene expression: as mRNAs, ribosome-nascent chain complexes, or complete precursor proteins.

  • While almost all proteins use the same entry gate to the mitochondria, before and after it they can embark on different targeting and import pathways.

  • Delays in mitochondrial protein import or mistargeting to other organelles affect cellular homeostasis; hence, cells have evolved specific mechanisms to sense and counteract such situations.

  • Cytosolic chaperones promote mitochondrial protein import under normal conditions, as well as play a major role in stress response pathways associated with mitochondrial protein import defects.

While targeting of proteins synthesized in the cytosol to any organelle is complex, mitochondria present the most challenging of destinations. First, import of nuclear-encoded proteins needs to be balanced with production of mitochondrial-encoded ones. Moreover, as mitochondria are divided into distinct subdomains, their proteins harbor a number of different targeting signals and biophysical properties. While translocation into the mitochondrial membranes has been well studied, the cytosolic steps of protein import remain poorly understood. Here, we review current knowledge on mRNA and protein targeting to mitochondria, as well as recent advances in our understanding of the cellular programs that respond to accumulation of mitochondrial precursor proteins in the cytosol, thus linking defects in targeting-capacity to signaling.

Keywords

mitochondrial protein import
RNA-binding proteins
nascent-chain associated complex
chaperones
mitochondrial precursor
mitochondrial targeting sequence

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