tetano
Editor, Senior Moderator
Immunity. 2016 May 23. pii: S1074-7613(16)30056-5. doi: 10.1016/j.immuni.2016.02.018. [Epub ahead of print]
[h=1]Fine-Tuning of CD8+ T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus.[/h] Champagne DP[SUP]1[/SUP], Hatle KM[SUP]1[/SUP], Fortner KA[SUP]1[/SUP], D'Alessandro A[SUP]2[/SUP], Thornton TM[SUP]1[/SUP], Yang R[SUP]1[/SUP], Torralba D[SUP]1[/SUP], Tom?s-Cort?zar J[SUP]3[/SUP], Jun YW[SUP]4[/SUP], Ahn KH[SUP]4[/SUP], Hansen KC[SUP]2[/SUP], Haynes L[SUP]5[/SUP], Anguita J[SUP]6[/SUP], Rincon M[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mitochondrial respiration is regulated in CD8[SUP]+[/SUP] T cells during the transition from naive to effector and memory cells, but mechanisms controlling this process have not been defined. Here we show that MCJ (methylation-controlled J protein) acted as an endogenous break for mitochondrial respiration in CD8[SUP]+[/SUP] T cells by interfering with the formation of electron transport chain respiratory supercomplexes. Metabolic profiling revealed enhanced mitochondrial metabolism in MCJ-deficient CD8[SUP]+[/SUP] T cells. Increased oxidative phosphorylation and subcellular ATP accumulation caused by MCJ deficiency selectively increased the secretion, but not expression, of interferon-γ. MCJ also adapted effector CD8[SUP]+[/SUP] T cell metabolism during the contraction phase. Consequently, memory CD8[SUP]+[/SUP] T cells lacking MCJ provided superior protection against influenza virus infection. Thus, MCJ offers a mechanism for fine-tuning CD8[SUP]+[/SUP] T cell mitochondrial metabolism as an alternative to modulating mitochondrial mass, an energetically expensive process. MCJ could be a therapeutic target to enhance CD8[SUP]+[/SUP] T cell responses.
Copyright ? 2016 Elsevier Inc. All rights reserved.
PMID: 27234056 [PubMed - as supplied by publisher]
[h=1]Fine-Tuning of CD8+ T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus.[/h] Champagne DP[SUP]1[/SUP], Hatle KM[SUP]1[/SUP], Fortner KA[SUP]1[/SUP], D'Alessandro A[SUP]2[/SUP], Thornton TM[SUP]1[/SUP], Yang R[SUP]1[/SUP], Torralba D[SUP]1[/SUP], Tom?s-Cort?zar J[SUP]3[/SUP], Jun YW[SUP]4[/SUP], Ahn KH[SUP]4[/SUP], Hansen KC[SUP]2[/SUP], Haynes L[SUP]5[/SUP], Anguita J[SUP]6[/SUP], Rincon M[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mitochondrial respiration is regulated in CD8[SUP]+[/SUP] T cells during the transition from naive to effector and memory cells, but mechanisms controlling this process have not been defined. Here we show that MCJ (methylation-controlled J protein) acted as an endogenous break for mitochondrial respiration in CD8[SUP]+[/SUP] T cells by interfering with the formation of electron transport chain respiratory supercomplexes. Metabolic profiling revealed enhanced mitochondrial metabolism in MCJ-deficient CD8[SUP]+[/SUP] T cells. Increased oxidative phosphorylation and subcellular ATP accumulation caused by MCJ deficiency selectively increased the secretion, but not expression, of interferon-γ. MCJ also adapted effector CD8[SUP]+[/SUP] T cell metabolism during the contraction phase. Consequently, memory CD8[SUP]+[/SUP] T cells lacking MCJ provided superior protection against influenza virus infection. Thus, MCJ offers a mechanism for fine-tuning CD8[SUP]+[/SUP] T cell mitochondrial metabolism as an alternative to modulating mitochondrial mass, an energetically expensive process. MCJ could be a therapeutic target to enhance CD8[SUP]+[/SUP] T cell responses.
Copyright ? 2016 Elsevier Inc. All rights reserved.
PMID: 27234056 [PubMed - as supplied by publisher]