Structure of the mature kinetoplastids mitoribosome and insights into its large subunit biogenesis

Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29851-29861. doi: 10.1073/pnas.2011301117. Epub 2020 Nov 9.


Kinetoplastids are unicellular eukaryotic parasites responsible for such human pathologies as Chagas disease, sleeping sickness, and leishmaniasis. They have a single large mitochondrion, essential for the parasite survival. In kinetoplastid mitochondria, most of the molecular machineries and gene expression processes have significantly diverged and specialized, with an extreme example being their mitochondrial ribosomes. These large complexes are in charge of translating the few essential mRNAs encoded by mitochondrial genomes. Structural studies performed in Trypanosoma brucei already highlighted the numerous peculiarities of these mitoribosomes and the maturation of their small subunit. However, several important aspects mainly related to the large subunit (LSU) remain elusive, such as the structure and maturation of its ribosomal RNA. Here we present a cryo-electron microscopy study of the protozoans Leishmania tarentolae and Trypanosoma cruzi mitoribosomes. For both species, we obtained the structure of their mature mitoribosomes, complete rRNA of the LSU, as well as previously unidentified ribosomal proteins. In addition, we introduce the structure of an LSU assembly intermediate in the presence of 16 identified maturation factors. These maturation factors act on both the intersubunit and the solvent sides of the LSU, where they refold and chemically modify the rRNA and prevent early translation before full maturation of the LSU.

Keywords: cryo-electron microscopy; kinetoplastids; mRNA translation; mitochondrial ribosome; ribosome biogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use
  • Chagas Disease / drug therapy
  • Chagas Disease / parasitology
  • Cryoelectron Microscopy
  • Humans
  • Leishmania / cytology
  • Leishmania / drug effects
  • Leishmania / physiology*
  • Leishmaniasis / drug therapy
  • Leishmaniasis / parasitology
  • Mitochondrial Ribosomes / drug effects
  • Mitochondrial Ribosomes / metabolism
  • Mitochondrial Ribosomes / ultrastructure*
  • Models, Molecular
  • RNA Processing, Post-Transcriptional / drug effects
  • RNA Processing, Post-Transcriptional / physiology*
  • RNA, Ribosomal / metabolism
  • Ribosomal Proteins / metabolism
  • Ribosome Subunits, Large, Eukaryotic / metabolism*
  • Ribosome Subunits, Large, Eukaryotic / ultrastructure
  • Trypanosoma cruzi / cytology
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / physiology*


  • Antiprotozoal Agents
  • RNA, Ribosomal
  • Ribosomal Proteins