title: The enigmatic role of tafazzin in cardiolipin metabolism.
abstract: 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.
authors.affiliation: University of Amsterdam, Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.forename: Marjolein
authors.initials: M
authors.lastname: Turkenburg
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
authors.forename: Daniela
authors.initials: D
authors.lastname: Karall
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Willem
authors.initials: W
authors.lastname: Kulik
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
mesh_terms: D000217:Acyltransferases; D002308:Cardiolipins / Q000378:metabolism*; D006801:Humans; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D002308:Cardiolipins; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human