期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 1, 页码 26-38出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.09.028
关键词
Necrotic cell death; Mitochondria; Lysosomes; Dictyostelium
资金
- Association pour la Recherche contre le Cancer, the Ministere de la Recherche
- ACI BCMS
- ACI Canceropole PACA
- Agence Nationale pour la Recherche (Programme non thematique Dicty Death)
- European Union (FP6 STREP TRANSDEATH)
Dicryostelium atg1- mutant cells provide an experimentally and genetically favorable model to study necrotic cell death (NCD) with no interference from apoptosis or autophagy. In such cells subjected to starvation and CAMP, induction by the differentiation-inducing factor DIF or by classical uncouplers led within minutes to mitochondrial uncoupling, which causally initiated NCD. We now report that (1) in this model, NCD included a mitochondrial-lysosomal cascade of events, (2) mitochondrial uncoupling and therefore initial stages of death showed reversibility for a surprisingly long time, (3) subsequent lysosomal permeabilization could be demonstrated using Lysosensor blue, acridin orange, Texas red-dextran and cathepsin B substrate, (4) this lysosomal permeabilization was irreversible, and (5) the presence of the uncoupler was required to maintain mitochondrial lesions but also to induce lysosomal lesions, suggesting that signaling from mitochondria to lysosomes must be sustained by the continuous presence of the uncoupler. These results further characterized the NCD pathway in this priviledged model, contributed to a definition of NCD at the lysosomal level, and suggested that in mammalian NCD even late reversibility attempts by removal of the inducer may be of therapeutic interest. (C) 2008 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据