Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death
An effective adaptive immune response requires rapid T cell proliferation, followed by equally robust cell death. These two processes are coordinately regulated to allow sufficient magnitude of response followed by its rapid resolution, while also providing the maintenance of T cell memory. Both asp...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00028/full |
| _version_ | 1819066845866491904 |
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| author | Michael A. Secinaro Karen A. Fortner Cheryl Collins Mercedes Rincón Ralph C. Budd |
| author_facet | Michael A. Secinaro Karen A. Fortner Cheryl Collins Mercedes Rincón Ralph C. Budd |
| author_sort | Michael A. Secinaro |
| collection | DOAJ |
| description | An effective adaptive immune response requires rapid T cell proliferation, followed by equally robust cell death. These two processes are coordinately regulated to allow sufficient magnitude of response followed by its rapid resolution, while also providing the maintenance of T cell memory. Both aspects of this T cell response are characterized by profound changes in metabolism; glycolysis drives proliferation whereas oxidative phosphorylation supports the survival of memory T cells. While much is known about the separate aspects of T cell expansion and contraction, considerably less is understood regarding how these processes might be connected. We report a link between the induction of glycolysis in CD8+ T cells and upregulation of the inhibitor of complex I and oxidative phosphorylation, methylation-controlled J protein (MCJ). MCJ acts synergistically with glycolysis to promote caspase-3 activity. Effector CD8+ T cells from MCJ-deficient mice manifest reduced glycolysis and considerably less active caspase-3 compared to wild-type cells. Consistent with these observations, in non-glycolytic CD8+ T cells cultured in the presence of IL-15, MCJ expression is repressed by methylation, which parallels their reduced active caspase-3 and increased survival compared to glycolytic IL-2-cultured T cells. Elevated levels of MCJ are also observed in vivo in the highly proliferative and glycolytic subset of CD4-CD8- T cells in Fas-deficient lpr mice. This subset also manifests elevated levels of activated caspase-3 and rapid cell death. Collectively, these data demonstrate tight linkage of glycolysis, MCJ expression, and active caspase-3 that serves to prevent the accumulation and promote the timely death of highly proliferative CD8+ T cells. |
| first_indexed | 2024-12-21T16:08:50Z |
| format | Article |
| id | doaj.art-53b3e9e2f92e4f2fa428c8859288ca61 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T16:08:50Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-53b3e9e2f92e4f2fa428c8859288ca612022-12-21T18:57:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-03-01710.3389/fcell.2019.00028432956Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and DeathMichael A. SecinaroKaren A. FortnerCheryl CollinsMercedes RincónRalph C. BuddAn effective adaptive immune response requires rapid T cell proliferation, followed by equally robust cell death. These two processes are coordinately regulated to allow sufficient magnitude of response followed by its rapid resolution, while also providing the maintenance of T cell memory. Both aspects of this T cell response are characterized by profound changes in metabolism; glycolysis drives proliferation whereas oxidative phosphorylation supports the survival of memory T cells. While much is known about the separate aspects of T cell expansion and contraction, considerably less is understood regarding how these processes might be connected. We report a link between the induction of glycolysis in CD8+ T cells and upregulation of the inhibitor of complex I and oxidative phosphorylation, methylation-controlled J protein (MCJ). MCJ acts synergistically with glycolysis to promote caspase-3 activity. Effector CD8+ T cells from MCJ-deficient mice manifest reduced glycolysis and considerably less active caspase-3 compared to wild-type cells. Consistent with these observations, in non-glycolytic CD8+ T cells cultured in the presence of IL-15, MCJ expression is repressed by methylation, which parallels their reduced active caspase-3 and increased survival compared to glycolytic IL-2-cultured T cells. Elevated levels of MCJ are also observed in vivo in the highly proliferative and glycolytic subset of CD4-CD8- T cells in Fas-deficient lpr mice. This subset also manifests elevated levels of activated caspase-3 and rapid cell death. Collectively, these data demonstrate tight linkage of glycolysis, MCJ expression, and active caspase-3 that serves to prevent the accumulation and promote the timely death of highly proliferative CD8+ T cells.https://www.frontiersin.org/article/10.3389/fcell.2019.00028/fullcaspase-3MCJglycolysisT cellscell death |
| spellingShingle | Michael A. Secinaro Karen A. Fortner Cheryl Collins Mercedes Rincón Ralph C. Budd Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death Frontiers in Cell and Developmental Biology caspase-3 MCJ glycolysis T cells cell death |
| title | Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death |
| title_full | Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death |
| title_fullStr | Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death |
| title_full_unstemmed | Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death |
| title_short | Glycolysis Induces MCJ Expression That Links T Cell Proliferation With Caspase-3 Activity and Death |
| title_sort | glycolysis induces mcj expression that links t cell proliferation with caspase 3 activity and death |
| topic | caspase-3 MCJ glycolysis T cells cell death |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00028/full |
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