The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.

中文翻译：

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JNK1 和 ERK1/2 在 AICD 诱导后通过 BIM 和 DRP1 调节淋巴细胞稳态。

激活诱导的细胞死亡 (AICD) 是一种依赖刺激的细胞凋亡形式，一旦炎症源被消除，机体就会使用它来关闭 T 细胞反应，同时允许产生免疫记忆。AICD 被认为是通过激活细胞死亡的外在 Fas/FasL 途径来进展的，导致通过 caspase-8 和 Bid 激活释放细胞色素-C。我们最近描述了在 AICD 诱导的早期，线粒体经历了结构改变，这是促进细胞色素 C 释放和执行细胞死亡所必需的。在这里，我们发现这种改变不依赖于 Fas/FasL 通路，它只是最近被激活以放大细胞死亡级联反应。相反，这种改变主要依赖于 MAPK 蛋白 JNK1 和 ERK1/2，反过来，调节促裂变蛋白 Drp1 和促凋亡因子 Bim 的活性。后者调节嵴解体并与 Drp1 协同介导线粒体外膜透化 (MOMP)，导致细胞色素 C 释放。有趣的是，我们发现 Bim 在 T 细胞急性淋巴细胞白血病 (T-ALL) 细胞中也被下调，这种改变有利于它们摆脱 AICD 介导的控制。