Structure of the Mammalian Mitochondrial Ribosome Reveals an Expanded Functional Role for Its Component Proteins

Abstract

The mitochondrial ribosome is responsible for the biosynthesis of protein components crucial to the generation of ATP in the eukaryotic cell. Because the protein:RNA ratio in the mitochondrial ribosome (approximately 69:approximately 31) is the inverse of that of its prokaryotic counterpart (approximately 33:approximately 67), it was thought that the additional and/or larger proteins of the mitochondrial ribosome must compensate for the shortened rRNAs. Here, we present a three-dimensional cryo-electron microscopic map of the mammalian mitochondrial 55S ribosome carrying a tRNA at its P site, and we find that instead, many of the proteins occupy new positions in the ribosome. Furthermore, unlike cytoplasmic ribosomes, the mitochondrial ribosome possesses intersubunit bridges composed largely of proteins; it has a gatelike structure at its mRNA entrance, perhaps involved in recruiting unique mitochondrial mRNAs; and it has a polypeptide exit tunnel that allows access to the solvent before the exit site, suggesting a unique nascent-polypeptide exit mechanism.

Proteomics and electron microscopic characterization of the unusual mitochondrial ribosome-related 45S complex in Leishmania tarentolae

“…This mass falls within the expected range for a complex with a sedimentation value of 45S. For comparison, the molecular mass of the 55S mammalian mitochondrial ribosome containing the 12S SSU rRNA, the 16S LSU rRNA and 77 proteins is 2.71 MDa [31].…”

“…Mitochondrial ribosomal proteins, as a rule, are significantly longer than their eubacterial counterparts [31][32][33][34][35][36][37][38]. This difference is due to the presence of N-or C-terminal extensions which were proposed to serve structural and/or functional compensation for the missing stemloop structures of the ribosomal RNAs [36], although this idea was not supported by the cryo-EM analysis of bovine mitoribosomes [31]. In Leishmania, the increase in length was due to long N-terminal extensions for several ribosomal proteins including S8, S9 and S11.…”

RMND1 deficiency associated with neonatal lactic acidosis, infantile onset renal failure, deafness, and multiorgan involvement

“…Mitochondrial and bacterial ribosomes share common drug sensitivities, but they are remarkably different structures; only about 40% of the mammalian ribosomal subunits have clear bacterial orthologues, and the RNA to protein ratio, which is about 2:1 in bacteria, is completely reversed (1:2) in mammals. 16 Mammalian mitochondrial ribosomes translate only 13 polypeptides, all of which are hydrophobic inner membrane proteins. These proteins are thought to be co-translationally inserted into the inner mitochondrial membrane as they emerge from the exit tunnel of the ribosome, but exactly how mitochondrial ribosomes are targeted and stabilized near the inner membrane is not known.…”

Terminating human mitochondrial protein synthesis: A shift in our thinking

“…Despite more than two decades of frustration, the field still lacks reliable and widely accepted methods of organellar transfection in intact cells and in vitro translation systems that would render us capable of asking more groups have documented just how significantly different this particle is, not only when compared to the bacterial 70S and the eukaryotic 80S ribosome but also in comparison to other mitochondrial ribosomes. [26][27][28][29] The normal ratio of ∼70% RNA to 30% protein is reversed, and this increased protein content affects the buoyant density and sedimentation value generating a 55S mitoribosome. Although the 55S and bacterial 70S particles have a similar mass, those of the mammalian organelle are larger and have a more porous structure.…”

“…This together with the fact that the mammalian 16S mt-rRNA has lost regions corresponding to the rRNA of the bacterial 70S ribosome that would contact the E-site tRNA, has led to the suggestion that these mitoribosomes lack an E-site (reviewed in ref. 26). This would have an impact on the ease of 55S frameshifting, as with an AGA or AGG in the A-site there would be only a single anti-codon/codon pairing in the P-site to break and reform.…”