Mitochondrial translation initiation machinery: Conservation and diversification

Abstract

The highly streamlined mitochondrial genome encodes almost exclusively a handful of transmembrane components of the respiratory chain complex. In order to ensure the correct assembly of the respiratory chain, the products of these genes must be produced in the correct stoichiometry and inserted into the membrane, posing a unique challenge to the mitochondrial translational system. In this review we describe the proteins orchestrating mitochondrial translation initiation: bacterial-like general initiation factors mIF2 and mIF3, as well as mitochondria-specific components – mRNA-specific translational activators and mRNA-nonspecific accessory initiation factors. We consider how the fast rate of evolution in these organelles has not only created a system that is divergent from that of its bacterial ancestors, but has led to a huge diversity in lineage specific mechanistic features of mitochondrial translation initiation among eukaryotes.

Regulation of mRNA Translation in Neurons—A Matter of Life and Death

“…Mitochondrial translation has several unique characteristics not observed in either prokaryotes or cytoplasmic translation in eukaryotes, including a distinct genetic code, uncapped mRNAs with short or non-existent 5’ untranslated regions (UTR), smaller and protein-rich ribosomes, and unique tRNAs. The topic of mitochondrial translation, and its involvement in disease has been the subject of several recent reviews, and will not be further discussed here (Boczonadi and Horvath, 2014; Kuzmenko et al, 2014; Mai et al, 2017; Pearce et al, 2013). …”

Mitochondrial methionyl N-formylation affects steady-state levels of oxidative phosphorylation complexes and their organization into supercomplexes

“…One interesting evolutionary question is whether mitochondria continue to rely on N-formylation for protein synthesis or whether they can function without it. Nformylation of Met-tRNA Met was already shown to be dispensable in certain bacteria, such as P. aeruginosa (7), and yeast (2) providing the first clue that, at least in lower eukaryotes, formylation of the mitochondrial initiator tRNA is not an absolute requirement. In mammals, bovine mitochondrial mtIF2 initiation factor strongly prefers N-formylated fMet-tRNA Met over non-formylated MettRNA Met (19,20).…”

“…In mammalian mitochondria, the initiation step acts as a major checkpoint and rate-limiting factor in protein synthesis (2). The nuclear-encoded protein methionyltRNA formyltransferase (MTFMT) is responsible for adding a formyl group to a portion of the single mitochondrial MettRNA Met (3).…”

“…The nuclear-encoded protein methionyltRNA formyltransferase (MTFMT) is responsible for adding a formyl group to a portion of the single mitochondrial MettRNA Met (3). Once the Met-tRNA is acylated/aminoacylated with methionine (MettRNA Met ) and N-formylated by MTFMT (fMet-tRNA Met ), it is recognized by the initiation factor mtIF2 (a translational GTPase), before it binds to the small mitoribosomal subunit (SSU)-mRNA complex (2,3). Following this, hydrolysis of GTP into GDP facilitates the binding of the large mitoribosomal subunit (LSU) and completes the formation of the initiation complex allowing elongation to start (4).…”

Going against the Tide: Selective Cellular Protein Synthesis during Virally Induced Host Shutoff

“…They are transcribed and located in distinct cellular compartments (27). Even more intriguing, the mRNAs are translated either in mitochondria (for mRNAs derived from mitochondrial genome) or the cytoplasm (for mRNAs derived from nuclear genome) using completely distinct translation machineries (28,29). How do these genes resist accelerated mRNA degradation or elevate translation efficiency in different cellular compartments?…”