Department of Biological Science, and Center for Applied Biotechnology Studies, California State University Fullerton, Fullerton, CA, 92831, USA.
Dept. of Biological Sciences, University of Pittsburgh, 519 Langley Hall, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA,
Front Biosci (Landmark Ed). 2017 Mar 1;22(8):1330-1343. doi: 10.2741/4546.
Lysosomes are emerging as important players in cellular zinc ion (Zn) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn handling. In addition to zinc transporters (ZnT) of the solute-carrier family type 30A (SLC30A), the lysosomal ion channel TRPML1 and the poorly understood novel transporter TMEM163 have been shown to play a role in the Zn uptake by the lysosomes. In this review, we summarize the current knowledge on molecular determinants of the lysosomal Zn handling, uptake, and release pathways, as well as discuss their possible roles in health and disease.
溶酶体正成为细胞内锌离子（Zn）稳态的重要参与者。关于神经元溶酶体中 Zn2+积累的一系列工作，以及越来越多的证据表明溶酶体 Zn 在乳腺退化过程中的细胞死亡中的作用，为溶酶体在细胞 Zn 处理中的核心作用奠定了生物学先例。这种作用一方面似乎涉及细胞保护，另一方面涉及细胞死亡。最近的一系列工作开始确定溶酶体 Zn 处理的分子决定因素。除溶质载体家族 30A（SLC30A）的锌转运体（ZnT）外，溶酶体离子通道 TRPML1 和了解甚少的新型转运体 TMEM163 已被证明在溶酶体摄取 Zn 中发挥作用。在这篇综述中，我们总结了目前关于溶酶体 Zn 处理、摄取和释放途径的分子决定因素的知识，并讨论了它们在健康和疾病中的可能作用。
