TY - JOUR
T1 - The enigmatic role of tafazzin in cardiolipin metabolism
AU - Houtkooper, Riekelt H.
AU - Turkenburg, Marjolein
AU - Poll-The, Bwee Tien
AU - Karall, Daniela
AU - Pérez-Cerdá, Celia
AU - Morrone, Amelia
AU - Malvagia, Sabrina
AU - Wanders, Ronald J.
AU - Kulik, Willem
AU - Vaz, Frédéric M.
PY - 2009
Y1 - 2009
N2 - The mitochondrial phospholipid cardiolipin plays an important role in cellular metabolism as exemplified by its involvement in mitochondrial energy production and apoptosis. Following its biosynthesis, cardiolipin is actively remodeled to achieve its final acyl composition. An important cardiolipin remodeling enzyme is tafazzin, of which several mRNA splice variants exist. Mutations in the tafazzin gene cause the X-linked recessive disorder Barth syndrome. In addition to providing an overview of the current knowledge in literature about tafazzin, we present novel experimental data and use this to discuss the functional role of the different tafazzin variants in cardiolipin metabolism in relation to Barth syndrome. We developed and performed specific quantitative PCR analyses of different tafazzin mRNA splice variants in 16 human tissues and correlated this with the tissue cardiolipin profile. In BTHS fibroblasts we showed that mutations in the tafazzin gene affected both the level and distribution of tafazzin mRNA variants. Transient expression of selected human tafazzin variants in BTHS fibroblasts showed for the first time in a human cell system that tafazzin lacking exon5 indeed functions in cardiolipin remodeling
AB - The mitochondrial phospholipid cardiolipin plays an important role in cellular metabolism as exemplified by its involvement in mitochondrial energy production and apoptosis. Following its biosynthesis, cardiolipin is actively remodeled to achieve its final acyl composition. An important cardiolipin remodeling enzyme is tafazzin, of which several mRNA splice variants exist. Mutations in the tafazzin gene cause the X-linked recessive disorder Barth syndrome. In addition to providing an overview of the current knowledge in literature about tafazzin, we present novel experimental data and use this to discuss the functional role of the different tafazzin variants in cardiolipin metabolism in relation to Barth syndrome. We developed and performed specific quantitative PCR analyses of different tafazzin mRNA splice variants in 16 human tissues and correlated this with the tissue cardiolipin profile. In BTHS fibroblasts we showed that mutations in the tafazzin gene affected both the level and distribution of tafazzin mRNA variants. Transient expression of selected human tafazzin variants in BTHS fibroblasts showed for the first time in a human cell system that tafazzin lacking exon5 indeed functions in cardiolipin remodeling
U2 - https://doi.org/10.1016/j.bbamem.2009.07.009
DO - https://doi.org/10.1016/j.bbamem.2009.07.009
M3 - Review article
C2 - 19619503
SN - 0005-2736
VL - 1788
SP - 2003
EP - 2014
JO - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
IS - 10
ER -