Cardiolipin deficiency in Barth syndrome is not associated with increased superoxide/H2 O2 production in heart and skeletal muscle mitochondria

FEBS Lett. 2021 Feb;595(3):415-432. doi: 10.1002/1873-3468.13973. Epub 2020 Nov 19.


Barth syndrome (BTHS) is a rare X-linked genetic disorder caused by mutations in the gene encoding the transacylase tafazzin and characterized by loss of cardiolipin and severe cardiomyopathy. Mitochondrial oxidants have been implicated in the cardiomyopathy in BTHS. Eleven mitochondrial sites produce superoxide/hydrogen peroxide (H2 O2 ) at significant rates. Which of these sites generate oxidants at excessive rates in BTHS is unknown. Here, we measured the maximum capacity of superoxide/H2 O2 production from each site and the ex vivo rate of superoxide/H2 O2 production in the heart and skeletal muscle mitochondria of the tafazzin knockdown mice (tazkd) from 3 to 12 months of age. Despite reduced oxidative capacity, superoxide/H2 O2 production was indistinguishable between tazkd mice and wild-type littermates. These observations raise questions about the involvement of mitochondrial oxidants in BTHS pathology.

Keywords: Barth syndrome; cardiomyopathy; mitochondria; mitochondrial reactive oxygen species; superoxide/H2O2; tafazzin; tazkd mice; ‘ex vivo’ rate of superoxide/H2O2 production.

Publication types

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

MeSH terms

  • Acyltransferases / deficiency
  • Acyltransferases / genetics*
  • Animals
  • Barth Syndrome / enzymology
  • Barth Syndrome / genetics*
  • Barth Syndrome / pathology
  • Cardiolipins / metabolism
  • Disease Models, Animal
  • Electron Transport Chain Complex Proteins
  • Gene Expression
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria, Heart / enzymology*
  • Mitochondria, Heart / pathology
  • Mitochondria, Muscle / enzymology*
  • Mitochondria, Muscle / pathology
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / pathology
  • Myocardium / enzymology*
  • Myocardium / pathology
  • NAD / metabolism
  • Oxygen Consumption / genetics
  • Superoxides / metabolism


  • Cardiolipins
  • Electron Transport Chain Complex Proteins
  • NAD
  • Superoxides
  • Hydrogen Peroxide
  • Acyltransferases
  • tafazzin protein, mouse