TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Jagirdar, Gayatri
A1  - Elsner, Matthias
A1  - Scharf, Christian
A1  - Simm, Stefan
A1  - Borucki, Katrin
A1  - Peter, Daniela
A1  - Lalk, Michael
A1  - Methling, Karen
A1  - Linnebacher, Michael
A1  - Krohn, Mathias
A1  - Wolke, Carmen
A1  - Lendeckel, Uwe
T1  - Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression
JF  - Frontiers in Genetics
N2  - 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 exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and—as proven for Δ5—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; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. 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.
KW  - -
KW  - Barth syndrome
KW  - cardiolipin
KW  - cellular proliferation
KW  - gene expression
KW  - tafazzin
KW  - Barth syndrome (BTHS)
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-65499
SN  - 1664-8021
SS  - 1664-8021
U6  - https://doi.org/10.3389/fgene.2022.931017
DO  - https://doi.org/10.3389/fgene.2022.931017
VL  - 13
SP  - 17
S1  - 17
PB  - Frontiers Media S.A.
CY  - Lausanne
ER  -