First Author | Faris R | Year | 2014 |
Journal | Biochim Biophys Acta | Volume | 1842 |
Issue | 10 | Pages | 1475-82 |
PubMed ID | 25066474 | Mgi Jnum | J:218479 |
Mgi Id | MGI:5617663 | Doi | 10.1016/j.bbalip.2014.07.009 |
Citation | Faris R, et al. (2014) Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine CD4(+) T cell metabolic activation. Biochim Biophys Acta 1842(10):1475-82 |
abstractText | Glycerol-3-phosphate acyltransferase-1 is the first rate limiting step in de novo glycerophospholipid synthesis. We have previously demonstrated that GPAT-1 deletion can significantly alter T cell function resulting in a T cell phenotype similar to that seen in aging. Recent studies have suggested that changes in the metabolic profile of T cells are responsible for defining specific effector functions and T cell subsets. Therefore, we determined whether T cell dysfunction in GPAT-1 (-/-) CD4(+) T cells could be explained by changes in cellular metabolism. We show here for the first time that GPAT-1 (-/-) CD4(+) T cells exhibit several key metabolic defects. Striking decreases in both the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) were observed in GPAT-1 (-/-) CD4(+) T cells following CD3/CD28 stimulation indicating an inherent cellular defect in energy production. In addition, the spare respiratory capacity (SRC) of GPAT-1 (-/-) CD4+ T cells, a key indicator of their ability to cope with mitochondrial stress was significantly decreased. We also observed a significant reduction in mitochondrial membrane potential in GPAT-1 (-/-) CD4(+) T cells compared to their WT counterparts, indicating that GPAT-1 deficiency results in altered or dysfunctional mitochondria. These data demonstrate that deletion of GPAT-1 can dramatically alter total cellular metabolism under conditions of increased energy demand. Furthermore, altered metabolic response following stimulation may be the defining mechanism underlying T cell dysfunction in GPAT-1 (-/-) CD4(+) T cells. Taken together, these results indicate that GPAT-1 is essential for the response to the increased metabolic demands associated with T cell activation. |