Mechanism of the elevation in cardiolipin during HeLa cell entry into the S-phase of the human cell cycle
| Autor: | Grant M. Hatch, Kristin Hauff, Dorota D. Linda |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
chemistry.chemical_classification
Cardiolipins Lymphoblast Phospholipid Cell Biology Citrate (si)-Synthase Cell cycle Carbohydrate metabolism Biology biology.organism_classification Biochemistry S Phase HeLa chemistry.chemical_compound Enzyme Glucose chemistry Biosynthesis Gene Expression Regulation Cardiolipin Humans RNA Messenger Molecular Biology HeLa Cells |
| Zdroj: | The Biochemical journal. 417(2) |
| ISSN: | 1470-8728 |
| Popis: | CL (cardiolipin) is a key phospholipid involved in ATP generation. Since progression through the cell cycle requires ATP we examined regulation of CL synthesis during S-phase in human cells and investigated whether CL or CL synthesis was required to support nucleotide synthesis in S-phase. HeLa cells were made quiescent by serum depletion for 24 h. Serum addition resulted in substantial stimulation of [methyl-3H]thymidine incorporation into cells compared with serum-starved cells by 8 h, confirming entry into the S-phase. CL mass was unaltered at 8 h, but increased 2-fold by 16 h post-serum addition compared with serum-starved cells. The reason for the increase in CL mass upon entry into S-phase was an increase in activity and expression of CL de novo biosynthetic and remodelling enzymes and this paralleled the increase in mitochondrial mass. CL de novo biosynthesis from D-[U-14C]glucose was elevated, and from [1,3-3H]glycerol reduced, upon serum addition to quiescent cells compared with controls and this was a result of differences in the selection of precursor pools at the level of uptake. Triascin C treatment inhibited CL synthesis from [1-14C]oleate but did not affect [methyl-3H]thymidine incorporation into HeLa cells upon serum addition to serum-starved cells. Barth Syndrome lymphoblasts, which exhibit reduced CL, showed similar [methyl-3H]thymidine incorporation into cells upon serum addition to serum-starved cells compared with cells from normal aged-matched controls. The results indicate that CL de novo biosynthesis is up-regulated via elevated activity and expression of CL biosynthetic genes and this accounted for the doubling of CL seen during S-phase; however, normal de novo CL biosynthesis or CL itself is not essential to support nucleotide synthesis during entry into S-phase of the human cell cycle. |
| Databáze: | OpenAIRE |
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