GATA3 controls mitochondrial biogenesis in primary human CD4 + T cells during DNA damage
GATA3 controls mitochondrial biogenesis in primary human CD4 + T cells during DNA damage
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GATA3 在 DNA 损伤期间控制原代人 CD4 T 细胞的线粒体生物合成
DOI：
10.1101/727479
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Callender L
中科院分区：
文献类型：
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作者：
Callender L
GATA3是一种谱系特异的转录因子，可促进CD4+T辅助2(Th2)细胞的分化，但也参与其他T细胞和非T细胞的免疫调节、增殖和维持等多种过程。在这里，我们展示了一种由CD4+T细胞利用的机制，通过GATA3和AMPK的作用来增加线粒体质量以应对DNA损伤。活化的AMPK在转录水平增加PPARG辅活化子1α(PPARGC1a或PgC1DNA蛋白)的表达，在翻译水平增加GATA3的表达，而α损伤则增加核因子红系相关因子2(NFE2L2或NRF2)的表达。Pgc1α、GATA3和NRF2复合体与ATR共同促进线粒体的生物发生。这些发现扩展了GATA3的多效性相互作用，并突出了GATA3靶向细胞操作在DNA损伤后干预CD4+T细胞活性和功能的可能性。
GATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4+T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4+T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1Aor PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4+T cell viability and function after DNA damage.