Cardiac mitochondrial structure and function in tafazzin-knockdown mice

Mitochondrion. 2018 Nov:43:53-62. doi: 10.1016/j.mito.2018.10.005. Epub 2018 Oct 30.

Abstract

Mutations in the tafazzin gene are the basis of Barth syndrome. The tafazzin protein is responsible for the synthesis of cardiolipin. Doxycycline-induced tafazzin-knockdown mice have been used as a model for Barth syndrome. In the current study, we examined subsarcolemmal and interfibrillar mitochondria from hearts of tafazzin-knockdown mice, focusing on mitochondrial ultrastructure, oxidative phosphorylation, electron transport chain complex activity, and phospholipid and supercomplex content. We then compared the result with mitochondrial pathology in Barth syndrome patients. Although tafazzin-knockdown mouse is a reasonable model for the study of Barth syndrome pathophysiology, it is not a precise simulacrum of the human condition.

Keywords: Barth syndrome; Cardiolipin; Electron microscopy; Electron transport chain; Monolysocardiolipin; Oxidative phosphorylation; Supercomplex.

Publication types

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

MeSH terms

  • Acyltransferases
  • Animals
  • Barth Syndrome / pathology*
  • Disease Models, Animal
  • Electron Transport
  • Female
  • Gene Knockdown Techniques*
  • Humans
  • Male
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Myocardium / pathology*
  • Oxidative Phosphorylation
  • Phospholipids / analysis
  • Transcription Factors / biosynthesis*

Substances

  • Phospholipids
  • Transcription Factors
  • Acyltransferases
  • tafazzin protein, mouse