Manipulating and elucidating mitochondrial gene expression with engineered proteins

Philos Trans R Soc Lond B Biol Sci. 2020 Jan 20;375(1790):20190185. doi: 10.1098/rstb.2019.0185. Epub 2019 Dec 2.

Abstract

Many conventional, modern genome engineering tools cannot be used to study mitochondrial genetics due to the unusual structure and physiology of the mitochondrial genome. Here, we review a number of newly developed, synthetic biology-based approaches for altering levels of mutant mammalian mitochondrial DNA and mitochondrial RNAs, including transcription activator-like effector nucleases, zinc finger nucleases and engineered RNA-binding proteins. These approaches allow researchers to manipulate and visualize mitochondrial processes and may provide future therapeutics. This article is part of the theme issue 'Linking the mitochondrial genotype to phenotype: a complex endeavour'.

Keywords: mitochondria; mitochondrial disease; mitochondrial restriction enzymes; mitochondrial transcription activator-life effectors nucleases; mitochondrial zinc finger nucleases; synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Gene Expression*
  • Genes, Mitochondrial / genetics*
  • Humans
  • Mammals / genetics
  • Mutation
  • Protein Engineering*
  • RNA, Mitochondrial / genetics*
  • RNA, Mitochondrial / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Synthetic Biology
  • Transcription Activator-Like Effector Nucleases / genetics
  • Transcription Activator-Like Effector Nucleases / metabolism
  • Zinc Finger Nucleases / genetics
  • Zinc Finger Nucleases / metabolism

Substances

  • DNA, Mitochondrial
  • RNA, Mitochondrial
  • RNA-Binding Proteins
  • Transcription Activator-Like Effector Nucleases
  • Zinc Finger Nucleases