Romani A, Marfella C, Lakshmanan M
Department of Physiology and Biophysis, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Thyroid. 1996 Oct;6(5):513-9. doi: 10.1089/thy.1996.6.513.
The in vitro addition of thyroid hormone to isolated rat heart or liver mitochondria induces the extrusion of approximately 2-4 nmol Mg2+/mg protein from both mitochondria preparations. The mobilization of Mg2+ is not accompanied by extrusion of matrix ATP or K+, or by mitochondria swelling, thus excluding that the phenomenon occurs through the nonspecific opening of the mitochondrial permeability transition pore. Moreover, the Mg2+ extrusion is completely prevented by bongkrekic acid, a membrane-permeant inhibitor of the adenine nucleotide translocase (AdNT), and by cyclosporine, which has also been reported to inhibit AdNT in a bongkrekate-like manner, operating at the matrix site of the translocase. By contrast, atractyloside, another specific inhibitor of AdNT that operates at the cytosolic site of the AdNT, only partially affects the Mg2+ mobilization (< 30% inhibition). These findings and the binding of 125I-labeled thyroid hormone to both the dimeric and monomeric moiety of AdNT support the hypothesis that AdNT can operate as a specific receptor for thyroid hormone in the mitochondria, and suggest that thyroid hormone operates at the matrix site of the translocase. In addition, these observations may imply that some of the so called "nongenomic effects" exerted by thyroid hormone on mitochondrial metabolism could occur through changes in the matrix content of Mg2+.
在离体大鼠心脏或肝脏线粒体中体外添加甲状腺激素，会导致两种线粒体制剂中每毫克蛋白质挤出约2 - 4纳摩尔的Mg2 +。Mg2 +的动员并不伴随着基质ATP或K +的挤出，也不伴随着线粒体肿胀，因此排除了这种现象是通过线粒体通透性转换孔的非特异性开放而发生的可能性。此外，米酵菌酸（一种腺嘌呤核苷酸转位酶（AdNT）的膜通透抑制剂）和环孢素完全阻止了Mg2 +的挤出，据报道环孢素也以类似米酵菌酸的方式抑制AdNT，作用于转位酶的基质位点。相比之下，阿特拉津（另一种作用于AdNT胞质位点的AdNT特异性抑制剂）仅部分影响Mg2 +的动员（抑制率<30%）。这些发现以及125I标记的甲状腺激素与AdNT的二聚体和单体部分的结合支持了以下假设：AdNT可作为线粒体中甲状腺激素的特异性受体发挥作用，并表明甲状腺激素作用于转位酶的基质位点。此外，这些观察结果可能意味着甲状腺激素对线粒体代谢产生的一些所谓“非基因组效应”可能是通过Mg2 +的基质含量变化而发生的。
