Mitochondrial Glycerol‐3‐Phosphate Acyltransferase‐Dependent Phospholipid Synthesis Modulates Phospholipid Mass and IL‐2 Production in Jurkat T Cells. Issue 3 (21st January 2016)

• Record Type: Journal Article
• Authors: Faris, Robert; Weber, Mary M.; Seeger, Drew R.; Cavazos, David; de Graffenried, Linda; Murphy, Eric J.; Jolly, Christopher A.
• Is Part Of: Lipids. Volume 51:Issue 3(2016)
• Page Start: 291
• Page End: 301
• Publication Date: 2016-01-21
• Subjects: Phospholipid analysis -- Analytical techniques -- Lipid analysis -- Mammalian lipid biochemistry -- General area -- Acyl‐CoA transferases -- Metabolism -- Lipid metabolism -- Immunology -- Physiology -- Signal transduction -- Phospholipids -- Specific lipids; Lipids -- Periodicals; Lipids -- Periodicals; Lipiden; Lipides -- Périodiques; 547.77
• DOI: 10.1007/s11745-016-4121-5
• Languages: English
• ISSNs: 0024-4201

Abstract

Abstract: Changes in glycerophospholipid metabolism with age and disease can have a profound effect on immune cell activation and effector function. We previously demonstrated that glycerol‐3‐phosphate acyltransferase‐1, the first and rate limiting step in de novo glycerophospholipid synthesis, plays a role in modulating murine T cell function. The resultant phenotype is characterized by decreased IL‐2 production, increased propensity toward apoptosis, and altered membrane glycerophospholipid mass similar to that of an aged T cell. Since T cells in previous experiments were harvested from GPAT‐1 −/− mice, questions remained as to what extent the macro environment of the model influenced the observed cellular phenotype. Therefore, we generated and phenotypically characterized a mitochondrial glycerol‐3‐phosphate acyltransferase (GPAM) deficient Jurkat T cell. Furthermore, this line was used to probe possible mechanisms by which GPAT‐1/GPAM regulates T cell function. We report here that many of the key dysfunctional characteristics of murine GPAT‐1 −/− T cells are recapitulated in the GPAMKD Jurkat T cell. We found striking decreased IL‐2 production along with altered phospholipid mass and increased incidence of apoptosis. Since PtdOH is an indirect downstream product of GPAM, we attempted to rescue IL‐2 production with PtdOH supplementation; however, this addition did not return IL‐2 production to normal levels. Interestingly, we did find significantly decreased Zap‐70 phosphorylation following stimulation, suggesting that GPAM deficiency may alter membrane based stimulatory signaling. These data show for the first time that GPAM deficiency results in an inherent defect in Jurkat T cell function and glycerophospholipid composition and that this defect cannot be rescued by addition of exogenous PtdOH.