The role of mitochondrial mRNA translation in cellular communication

J Cell Sci. 2025 May 1;138(9):jcs263753. doi: 10.1242/jcs.263753. Epub 2025 May 6.

Abstract

Mitochondria are dynamic and heterogeneous organelles that rewire their network and metabolic functions in response to changing cellular needs. To this end, mitochondria integrate a plethora of incoming signals to influence cell fate and survival. A crucial and highly regulated node of cell-mitochondria communication is the translation of nuclear-encoded mitochondrial mRNAs. By controlling and monitoring the spatio-temporal translation of these mRNAs, cells can rapidly adjust mitochondrial function to meet metabolic demands, optimise ATP production and regulate organelle biogenesis and turnover. In this Review, we focus on how RNA-binding proteins that recognise nuclear-encoded mitochondrial mRNAs acutely modulate the rate of translation in response to nutrient availability. We further discuss the relevance of localised translation of these mRNAs for subsets of mitochondria in polarised cells. Finally, we highlight quality control mechanisms that monitor the translation process at the mitochondrial surface and their connections to mitophagy and stress responses. We propose that these processes collectively contribute to mitochondrial specialisation and signalling function.

Keywords: Cell signalling; Mitochondria; RNA-binding proteins; Ribosome quality control; Translation; mRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Communication* / genetics
  • Humans
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Mitophagy / genetics
  • Protein Biosynthesis*
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA, Mitochondrial* / genetics
  • RNA, Mitochondrial* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • RNA, Messenger
  • RNA, Mitochondrial
  • mitochondrial messenger RNA
  • RNA-Binding Proteins