Lossi Laura
Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, I-10095 Grugliasco, Torino, Italy.
Biochem J. 2022 Feb 11;479(3):357-384. doi: 10.1042/BCJ20210854.
Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.
程序性细胞死亡是多细胞生物体中维持组织稳态并清除潜在危险细胞的重要动态过程。凋亡是一种广为人知的程序性细胞死亡形式，当细胞表面死亡受体（如Fas）被其配体激活时（外源性途径），或者当BCL-2家族促凋亡蛋白导致线粒体外膜通透性改变时（内源性途径），凋亡就会被激活。凋亡的内源性和外源性途径都会导致一类蛋白酶（即半胱天冬酶）的激活，这些蛋白酶在凋亡的所谓执行阶段负责最终的细胞死亡。在这篇综述中，我将首先基于形态学讨论最常见的程序性细胞死亡类型。然后我将详细探讨内源性和外源性凋亡的分子途径，讨论它们如何响应特定刺激而被激活，以及它们有时是如何重叠的。深入了解凋亡的细胞机制不仅在细胞和分子生物学领域变得越来越重要，而且因其在包括神经退行性变和癌症在内的多种疾病中的转化潜力也日益重要。
