Re-expression of tafazzin isoforms in TAZ-deficient C6 glioma cells restores cardiolipin composition but not proliferation rate and alterations in gene expression

Tafazzin an acyltransferase is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exists in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study is to investigate if isoform Δ5, which is lacking exon 5, full length rat TAZ, and mutant full-length rat Taz (enzymatically dead H69L) could restore wild type phenotype in C6 TAZ cells with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aim to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells can fully restore CL composition and – as proven for 5 – this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZmut3). The re-expression of none of the TAZ isoforms used led to the restoration of the proliferation rate and gene expression profiles. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible. C6 (3 pooled samples) and C6 TAZ (3 pooled samples)