Intrinsically disordered proteins in human mitochondria

Masahiro Ito1, Yukako Tohsato, Hitoshi Sugisawa

  • 1Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.

Insights

Intrinsically disordered proteins (IDPs) are less common in mitochondria than in eukaryotes, with bacterial-like proteins showing lower disorder than host-derived ones. This suggests evolutionary origin, not location, influences IDP prevalence in mitochondria.

Area of Science:

  • Mitochondrial Biology
  • Protein Science
  • Evolutionary Biology

Background:

  • Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes but rare in prokaryotes.
  • Mitochondria, originating from α-proteobacteria, represent an evolutionary link between prokaryotes and eukaryotes.
  • The abundance of IDPs within mitochondria requires clarification due to their unique evolutionary position.

Purpose of the Study:

  • To investigate the prevalence and characteristics of intrinsically disordered proteins (IDPs) in human mitochondria.
  • To determine if the evolutionary origin of mitochondrial proteins influences their intrinsic disorder content.
  • To compare IDP levels in mitochondrially-encoded proteins versus host-encoded proteins within mitochondria.

Main Methods:

  • Retrieved 706 human mitochondrial proteins from UniProt.
  • Extracted intrinsically disordered region information using the DICHOT database.
  • Performed BLAST searches against α-proteobacterial proteins to classify mitochondrial proteins into bacterial-descended (B-type) and host-derived (E-type).

Main Results:

  • Identified 387 B-type and 319 E-type mitochondrial proteins.
  • Observed significantly lower average ID ratios in B-type proteins (10.3%) compared to E-type proteins (21.4%).
  • Found no strong correlation between mitochondrial subcompartment and IDP ratios, suggesting evolutionary origin is a key factor.

Conclusions:

  • The evolutionary origin of mitochondrial proteins significantly impacts their intrinsic disorder content.
  • Bacterial-derived mitochondrial proteins exhibit less intrinsic disorder than those acquired later from the host.
  • Intrinsic disorder prevalence in mitochondria is primarily shaped by evolutionary history rather than functional localization.

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