Identification and functional characterization of hCLS1, a human cardiolipin synthase localized in mitochondria
- 15 August 2006
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 398 (2), 169-176
- https://doi.org/10.1042/bj20060303
Abstract
In eukaryotic cells, CLS (cardiolipin synthase) is involved in the final step of cardiolipin synthesis by catalysing the transfer of a phosphatidyl residue from CDP-DAG (diacylglycerol) to PG (phosphatidylglycerol). Despite an important role of cardiolipin in regulating mitochondrial function, a gene encoding the mammalian CLS has not been identified so far. We report in the present study the identification and characterization of a human cDNA encoding the first mammalian CLS [hCLS1 (human CLS1)]. The predicted hCLS1 peptide sequence shares significant homology with the yeast and plant CLS proteins. The recombinant hCLS1 enzyme expressed in COS-7 cells catalysed efficiently the synthesis of cardiolipin in vitro using CDP-DAG and PG as substrates. Furthermore, overexpression of hCLS1 cDNA in COS-7 cells resulted in a significant increase in cardiolipin synthesis in intact COS-7 cells without any significant effects on the activity of the endogenous phosphatidylglycerophosphate synthase of the transfected COS-7 cells. Immunohistochemical analysis demonstrated that the recombinant hCLS1 protein was localized to the mitochondria when transiently expressed in COS-7 cells, which was further corroborated by results from subcellular fractionation analyses of the recombinant hCLS1 protein. Northern-blot analysis showed that the hCLS1 gene was predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism, with the highest expression in skeletal and cardiac muscles. High levels of hCLS1 expression were also detected in liver, pancreas, kidney and small intestine, implying a functional role of hCLS1 in these tissues.This publication has 33 references indexed in Scilit:
- Identification and characterization of human cardiolipin synthaseFEBS Letters, 2006
- Identification of an Arabidopsis thaliana gene for cardiolipin synthase located in mitochondriaFEBS Letters, 2004
- A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in MousePublished by Elsevier BV ,2004
- Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipinAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Cardiolipin Is Not Required to Maintain Mitochondrial DNA Stability or Cell Viability for Saccharomyces cerevisiae Grown at Elevated TemperaturesPublished by Elsevier BV ,2003
- Regulation of cell death: the calcium–apoptosis linkNature Reviews Molecular Cell Biology, 2003
- Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipinThe FASEB Journal, 2003
- Cardiolipin and apoptosisBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2002
- Mitochondrial decay in agingBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Thyroxine stimulates phosphatidylglycerolphosphate synthase activity in rat heart mitochondriaBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1995