Stomatin-like protein 2 deficiency in T cells is associated with altered mitochondrial respiration and defective CD4+ T cell responses.
J Immunol
; 189(9): 4349-60, 2012 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23028053
ABSTRACT
Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1ß subcomplex subunit 8, and NADH dehydrogenase (ubiquinone) 1α subcomplex subunit 9 of respiratory complex I, and decreased activity of this complex as well as of complex II plus III of the respiratory chain. In addition, SLP-2-deficient T cells showed a significant increase in uncoupled mitochondrial respiration and a greater reliance on glycolysis. Based on these results, we propose that SLP-2 organizes the mitochondrial membrane compartmentalization of cardiolipin, which is required for optimal assembly and function of respiratory chain complexes. This function, in T cells, helps to ensure proper metabolic response during activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sanguíneas
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Linfócitos T CD4-Positivos
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Subpopulações de Linfócitos T
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Doenças Mitocondriais
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Proteínas de Membrana
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article