Zn2+ efflux through lysosomal exocytosis prevents Zn2+-induced toxicity
Zn2+ efflux through lysosomal exocytosis prevents Zn2+-induced toxicity
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DOI：
10.1242/jcs.145318
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发表时间：
2014-07-15
影响因子：
4
通讯作者：
Kiselyov, Kirill
中科院分区：
文献类型：
--
作者：
Kukic, Ira;Kelleher, Shannon L.;Kiselyov, Kirill
Zn2+ is an essential micronutrient and an important ionic signal whose excess, as well as scarcity, is detrimental to cells. Free cytoplasmic Zn2+ is controlled by a network of Zn2+ transporters and chelating proteins. Recently, lysosomes became the focus of studies in Zn2+ transport, as they were shown to play a role in Zn2+-induced toxicity by serving as Zn2+ sinks that absorb Zn2+ from the cytoplasm. Here, we investigated the impact of the lysosomal Zn2+ sink on the net cellular Zn2+ distribution and its role in cell death. We found that lysosomes played a cytoprotective role during exposure to extracellular Zn2+. Such a role required lysosomal acidification and exocytosis. Specifically, we found that the inhibition of lysosomal acidification using Bafilomycin A1 (Baf) led to a redistribution of Zn2+ pools and increased apoptosis. Additionally, the inhibition of lysosomal exocytosis through knockdown (KD) of the lysosomal SNARE proteins VAMP7 and synaptotagmin VII (SYT7) suppressed Zn2+ secretion and VAMP7 KD cells had increased apoptosis. These data show that lysosomes play a central role in Zn2+ handling, suggesting that there is a new Zn2+ detoxification pathway.
