Mitochondrial Ribosomes in Cancer

Semin Cancer Biol. 2017 Dec;47:67-81. doi: 10.1016/j.semcancer.2017.04.004. Epub 2017 Apr 23.

Abstract

Mitochondria play fundamental roles in the regulation of life and death of eukaryotic cells. They mediate aerobic energy conversion through the oxidative phosphorylation (OXPHOS) system, and harbor and control the intrinsic pathway of apoptosis. As a descendant of a bacterial endosymbiont, mitochondria retain a vestige of their original genome (mtDNA), and its corresponding full gene expression machinery. Proteins encoded in the mtDNA, all components of the multimeric OXPHOS enzymes, are synthesized in specialized mitochondrial ribosomes (mitoribosomes). Mitoribosomes are therefore essential in the regulation of cellular respiration. Additionally, an increasing body of literature has been reporting an alternative role for several mitochondrial ribosomal proteins as apoptosis-inducing factors. No surprisingly, the expression of genes encoding for mitoribosomal proteins, mitoribosome assembly factors and mitochondrial translation factors is modified in numerous cancers, a trait that has been linked to tumorigenesis and metastasis. In this article, we will review the current knowledge regarding the dual function of mitoribosome components in protein synthesis and apoptosis and their association with cancer susceptibility and development. We will also highlight recent developments in targeting mitochondrial ribosomes for the treatment of cancer.

Keywords: Apoptosis; Cancer; Mitochondrial ribosomes; Therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Ribosomes / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Oxidative Phosphorylation
  • Protein Biosynthesis / drug effects
  • Ribosomal Proteins / metabolism
  • Signal Transduction / drug effects

Substances

  • Biomarkers
  • Ribosomal Proteins