Abstract

The translocases of the mitochondrial outer and inner membranes, the TOM and TIMs, import hundreds of nucleus-encoded proteins into mitochondria. TOM and TIMs are multi-subunit protein complexes that work in cooperation with other complexes to import proteins in different sub-mitochondrial destinations. The overall architecture of these protein complexes is conserved among yeast/fungi, animals, and plants. Recent studies have revealed unique characteristics of this machinery, particularly in the eukaryotic supergroup Excavata. Despite multiple differences, homologues of Tim17, an essential component of one of the TIM complexes and a member of the Tim17/Tim22/Tim23 family, have been found in all eukaryotes. Here, we review the structure and function of Tim17 and Tim17-containing protein complexes in different eukaryotes, and then compare them to the single homologue of this protein found in Trypanosoma brucei, a unicellular parasitic protozoan.

Highlights

  • Mitochondria, the essential organelles in eukaryotes, perform various cellular functions

  • We showed that TbTim17 was essential and involved in mitochondrial protein import in two major developmental stages of T. brucei [71]

  • Some confusion exists as to whether trypanosomatid Tim17 is a true homologue of the canonical Tim17 or Tim22 of fungi/yeast, we showed that ScTim17 could complement partially the growth defect of T. brucei caused by TbTim17 RNAi, as ScTim17 was targeted properly into mitochondria and assembled into the TbTim17 protein complex, whereas ScTim23 was imported into T. brucei mitochondria but not associated with TbTim17

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Summary

Introduction

Mitochondria, the essential organelles in eukaryotes, perform various cellular functions. The aqueous matrix houses the remnant genome of the eubacterial endosymbiont, which encodes only 1% of proteins required for the organellar function. Most of the mitochondrial proteins are coded in the host nuclear genome. These proteins are translated on cytosolic ribosomes and imported into various sub-mitochondrial locations via different receptor/translocase complexes in the MOM, MIM, and IMS [8,9]. The import of nucleus-encoded proteins into mitochondria is a conserved phenomenon among eukaryotes. The mitochondrial remnants, known as mitosomes and hydrogenosomes, found in some unicellular anerobic eukaryotes, including Entamoeba, Giardia, and Trichomonads species, respectively, import proteins from the cytosol to perform their functions [10]

Mitochondrial Protein Import Machinery
Prevalence of Tim17 and Tim17 Homologues Among Eukaryotes
Tim17 and Tim17-Containing Protein Complexes in Different Eukaryotes
Tim17 Structure
Biogenesis of Tim17
Role of Tim17 in Mitochondrial Stress Response
Connection of Tim17 Expression with Cancer
Findings
Conclusions
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