Emerging mechanisms of human mitochondrial translation regulation

Abstract

Mitochondrial translation regulation enables precise control over the synthesis of hydrophobic proteins encoded by the organellar genome, orchestrating their membrane insertion, accumulation, and assembly into oxidative phosphorylation (OXPHOS) complexes. Recent research highlights regulation across all translation stages (initiation, elongation, termination, and recycling) through a complex interplay of mRNA structures, specialized translation factors, and unique regulatory mechanisms that adjust protein levels for stoichiometric assembly. Key discoveries include mRNA-programmed ribosomal pausing, frameshifting, and termination-dependent re-initiation, which fine-tune protein synthesis and promote translation of overlapping open reading frames (ORFs) in bicistronic transcripts. In this review, we examine these advances, which are significantly enhancing our understanding of mitochondrial gene expression.

Keywords: RNA folding; mitochondrial translation; programmed ribosomal frameshifting; ribosome stalling; termination-reinitiation.