J Integr Plant Biol.

• Research Article •    

Translation rate underpins specific targeting of N‐terminal transmembrane proteins to mitochondria

Junho Lee1†, Byeongho Moon1†, Dong Wook Lee2,3 and Inhwan Hwang1*   

  1. 1. Department of Life Science, Pohang University of Science and Technology, Pohang 790‐784, South Korea
    2. Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, South Korea
    3. Department Bioenergy Science and Technology, Chonnam National University, Gwangju 61186, South Korea
    These two authors contributed equally to this work.
    *Correspondence: Inhwan Hwang (ihhwang@postech.ac.kr)
  • Received:2022-12-06 Accepted:2023-03-02 Online:2023-04-10

Abstract: Protein biogenesis is a complex process, and complexity is greatly increased in eukaryotic cells through specific targeting of proteins to different organelles. To direct targeting, organellar proteins carry an organelle-specific targeting signal for recognition by organelle-specific import machinery. However, the situation is confusing for transmembrane domain (TMD)-containing signal-anchored (SA) proteins of various organelles because TMDs function as an endoplasmic reticulum (ER) targeting signal. Although ER targeting of SA proteins is well understood, how they are targeted to mitochondria and chloroplasts remains elusive. Here, we investigated how the targeting specificity of SA proteins is determined for specific targeting to mitochondria and chloroplasts. Mitochondrial targeting requires multiple motifs around and within TMDs: a basic residue and an arginine-rich region flanking the N- and C-termini of TMDs, respectively, and an aromatic residue in the C-terminal side of the TMD that specify mitochondrial targeting in an additive manner. These motifs play a role in slowing down the elongation speed during translation, thereby ensuring mitochondrial targeting in a co-translational manner. By contrast, the absence of any of these motifs individually or together causes at varying degrees chloroplast targeting that occurs in a post-translational manner.

Key words: arginine‐rich region, ER targeting, mitochondria targeting, organelle targeting, TMD, translational slowdown, transmembrane domain

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