受调控的细胞死亡（Regulated cell death，RCD）控制着可有可无的、感染的或恶性细胞的去除，因此对多细胞生物的发育、稳态和免疫起着重要作用。在过去几年中，描述了不同形式的RCD（其中包括凋亡、坏死样凋亡、火焰凋亡和铁死亡），并且已经在分子水平上表征了控制它们诱导和执行的细胞信号通路。同时，已经明确不同形式的RCD在引发炎症或免疫反应方面存在差异，并且RCD通路显示出了显著的可塑性。生化和遗传学研究揭示，抑制给定的通路通常导致备用细胞死亡机制的激活，突显了基于共享信号组分和多价信号平台的紧密互连。由于这种互连性和“经典”细胞死亡诱导剂的多向效应，难以独立研究RCD通路。这促使发展基于合成生物学的工具，利用化学遗传学或光遗传学方法，有针对性地诱导RCD。在这里，我们讨论了这类工具集的最新进展，重点介绍了它们的优势和局限性，并阐述了它们在细胞和动物RCD研究中的应用。Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulated cell death (RCD) controls the removal of dispensable, infected or malignant cells, and is thus essential for development, homeostasis and immunity of multicellular organisms. Over the last years different forms of RCD have been described (among them apoptosis, necroptosis, pyroptosis and ferroptosis), and the cellular signaling pathways that control their induction and execution have been characterized at the molecular level. It has also become apparent that different forms of RCD differ in their capacity to elicit inflammation or an immune response, and that RCD pathways show a remarkable plasticity. Biochemical and genetic studies revealed that inhibition of a given pathway often results in the activation of back-up cell death mechanisms, highlighting close interconnectivity based on shared signaling components and the assembly of multivalent signaling platforms that can initiate different forms of RCD. Due to this interconnectivity and the pleiotropic effects of 'classical' cell death inducers, it is challenging to study RCD pathways in isolation. This has led to the development of tools based on synthetic biology that allow the targeted induction of RCD using chemogenetic or optogenetic methods. Here we discuss recent advances in the development of such toolset, highlighting their advantages and limitations, and their application for the study of RCD in cells and animals.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.