Whereas the apoptosis cell death pathway typically enables cells to undergo death in an immunologically silent manner, cell death by necroptosis induces cell lysis and release of cellular constituents known to elicit an immune response. Consequently, the origins of necroptosis likely originated in host defense against pathogens, although recently it has emerged that dysregulation of the pathway underlies many human pathologies. The past decade has seen a rapid advance in our understanding of the molecular mechanisms underlying necroptotic cell death, including the implication of the pseudokinase, mixed lineage kinase domain-like protein (MLKL), as the terminal effector in the pathway. Here, I review our current understanding of how MLKL is activated by the upstream receptor interacting protein kinase (RIPK)3, the proposed mechanism(s) by which MLKL kills cells, and recently described layers of regulation that tune MLKL's killing activity.

中文翻译：

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杀伤性假激酶混合谱系激酶域样蛋白 (MLK​​L)。

虽然细胞凋亡细胞死亡途径通常使细胞能够以免疫沉默的方式经历死亡，但由坏死性凋亡引起的细胞死亡诱导细胞裂解和已知可引发免疫反应的细胞成分的释放。因此，坏死性凋亡的起源可能起源于宿主对病原体的防御，尽管最近发现该途径的失调是许多人类病理的基础。在过去的十年中，我们对坏死性细胞死亡的分子机制的理解取得了快速进展，包括假激酶、混合谱系激酶结构域样蛋白 (MLK​​L) 作为通路中的末端效应子的含义。在这里，我回顾了我们目前对 MLKL 如何被上游受体相互作用蛋白激酶 (RIPK)3 激活的理解，