Mitochondrial protein import - Functional analysis of the highly diverged Tom22 orthologue of Trypanosoma brucei

Sci Rep. 2017 Jan 17:7:40738. doi: 10.1038/srep40738.


The β-barrel protein Tom40 and the α-helically anchored membrane protein Tom22 are the only universally conserved subunits of the protein translocase of the mitochondrial outer membrane (TOM). Tom22 has an N-terminal cytosolic and a C-terminal intermembrane space domain. It occurs in two variants: one typified by the yeast protein which has a cytosolic domain containing a cluster of acidic residues, and a shorter variant typified by the plant protein that lacks this domain. Yeast-type Tom22 functions as a secondary protein import receptor and is also required for the stability of the TOM complex. Much less is known about the more widespread short variant of Tom22, which is also found in the parasitic protozoan Trypanosoma brucei. Here we show that the intermembrane space domain of trypanosomal Tom22 binds mitochondrial precursor proteins and that it is essential for normal growth and mitochondrial protein import. Moreover, complementation experiments indicate that the intermembrane space domain cannot be replaced by the corresponding regions of the yeast or plant Tom22 orthologues. Lack or replacement of the short cytosolic domain, however, does not interfere with protein function. Finally, we show that only the membrane-spanning domain of trypanosomal Tom22 is essential for assembly of the trypanosomal TOM complex analogue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Checkpoints / genetics
  • Fungal Proteins
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Plant Proteins
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Precursors
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Protein Transport
  • RNA Interference
  • Trypanosoma brucei brucei / genetics
  • Trypanosoma brucei brucei / metabolism*


  • Fungal Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • Plant Proteins
  • Protein Precursors
  • Protein Subunits