Exogenous cardiolipin localizes to mitochondria and prevents TAZ knockdown-induced apoptosis in myeloid progenitor cells
| Autor: | Fong-Fu Hsu, Betty Su, Trudy M. Forte, Nikita Ikon, Robert O. Ryan |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cardiolipins
Biophysics Tafazzin Apoptosis HL-60 Cells Mitochondrion Biochemistry Article chemistry.chemical_compound Cardiolipin medicine Humans Annexin A5 Progenitor cell Molecular Biology Myeloid Progenitor Cells Gene knockdown biology Barth syndrome Cell Biology medicine.disease Mitochondria Cell biology chemistry Gene Knockdown Techniques biology.protein Acyltransferases HeLa Cells Protein Binding Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 464:580-585 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.07.012 |
| Popis: | The concentration and composition of cardiolipin (CL) in mitochondria are altered in age-related heart disease, Barth Syndrome, and other rare genetic disorders, resulting in mitochondrial dysfunction. To explore whether exogenous CL can be delivered to cells, CL was combined with apolipoprotein A-I to generate water-soluble, nanoscale complexes termed nanodisks (ND). Mass spectrometry of HL60 myeloid progenitor cell extracts revealed a 30-fold increase in cellular CL content following incubation with CL-ND. When CL-ND containing a fluorescent CL analogue was employed, confocal microscopy revealed CL localization to mitochondria. The ability of CL-ND to elicit a physiological response was examined in an HL60 cell culture model of Barth Syndrome neutropenia. siRNA knockdown of the phospholipid transacylase, tafazzin (TAZ), induced apoptosis in these cells. When TAZ knockdown cells were incubated with CL-ND, the apoptotic response was attenuated. Thus, CL-ND represent a potential intervention strategy for replenishment of CL in Barth Syndrome, age-related heart disease, and other disorders characterized by depletion of this key mitochondrial phospholipid. |
| Databáze: | OpenAIRE |
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