title: Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine CD4(+) T cell metabolic activation.
abstract: 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.
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
authors: Robert
authors: R
authors: Faris
authors: Program in Integrative Nutrition & Complex Diseases, Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, USA.
authors: Yang-Yi
authors: YY
authors: Fan
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
authors: Alejandra
authors: A
authors: De Angulo
authors: Program in Integrative Nutrition & Complex Diseases, Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, USA.
authors: Robert S
authors: RS
authors: Chapkin
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
authors: Linda A
authors: LA
authors: deGraffenried
authors: Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA. Electronic address: jolly@austin.utexas.edu.
authors: Christopher A
authors: CA
authors: Jolly
keywords: Fatty acid; Metabolism; Mouse; Oxidation; Phospholipid; T cell