Gincel Dan, Shoshan-Barmatz Varda
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
J Bioenerg Biomembr. 2004 Apr;36(2):179-86. doi: 10.1023/b:jobb.0000023621.72873.9e.
The amino acid glutamate, synthesized in the mitochondria, serves multiple functions, including acting as a neurotransmitter and participating in degradative and synthetic pathways. We have previously shown that glutamate modulates the channel activity of bilayer-reconstituted voltage-dependent anion channel (VDAC). In this study, we demonstrate that glutamate also modulates the opening of the mitochondrial permeability transition pore (PTP), of which VDAC is an essential component. Glutamate inhibited PTP opening, as monitored by transient Ca2+ accumulation, mitochondrial swelling and accompanying release of cytochrome c. Exposure to L-glutamate delayed the onset of PTP opening up to 3-times longer, with an IC50 of 0.5 mM. Inhibition of PTP opening by L-glutamate is highly specific, not being mimicked by D-glutamate, L-glutamine, L-aspartate, or L-asparagine. The interaction of L-glutamate with VDAC and its inhibition of VDAC's channel activity and PTP opening suggest that glutamate may also act as an intracellular messenger in the mitochondria-mediated apoptotic pathway.
在 mitochondria 中合成的氨基酸谷氨酸发挥多种功能，包括作为神经递质以及参与降解和合成途径。我们之前已表明谷氨酸可调节双层重构电压依赖性阴离子通道（VDAC）的通道活性。在本研究中，我们证明谷氨酸还可调节线粒体通透性转换孔（PTP）的开放，而 VDAC 是其重要组成部分。通过瞬时 Ca2+ 积累、线粒体肿胀以及伴随的细胞色素 c 释放监测发现，谷氨酸抑制 PTP 开放。暴露于 L-谷氨酸可将 PTP 开放的起始延迟长达 3 倍，IC50 为 0.5 mM。L-谷氨酸对 PTP 开放的抑制具有高度特异性，D-谷氨酸、L-谷氨酰胺、L-天冬氨酸或 L-天冬酰胺无法模拟这种抑制作用。L-谷氨酸与 VDAC 的相互作用及其对 VDAC 通道活性和 PTP 开放的抑制表明，谷氨酸可能还作为线粒体介导的凋亡途径中的细胞内信使发挥作用。
