Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer
Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer
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DOI：
10.1073/pnas.152259999
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发表时间：
2002-07-23
影响因子：
11.1
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Dzeja, PP;Bortolon, R;Terzic, A
细胞核和细胞质之间的信息交换取决于细胞的代谢状态，但核区室的能量供应途径尚不清楚。在这里，核质通讯的能量是通过组成性核蛋白组蛋白 H1 的成像输入来确定的。 H1 通过心脏细胞核孔的易位依赖于线粒体氧化磷酸化提供的 ATP，而不是糖酵解提供的 ATP。尽管线粒体聚集在细胞核周围，减少了能量转移的距离，但简单的核苷酸扩散不足以满足核运输的能量需求。相反，整合的磷酸转移网络是将高能磷酸基从线粒体传递到细胞核所必需的。在肌酸激酶活性较低的新生儿心肌细胞中，抑制腺苷酸激酶催化的磷酸转移可消除核输入。由于腺苷酸激酶缺陷，确保 ATP 和 GTP 之间磷酰基交换的核苷二磷酸激酶无法维持核输入。肌酸激酶磷酸转移的上调可模拟成体心肌细胞的代谢条件，从而挽救了 H1 的输入，这表明细胞能量系统的发育可塑性。因此，线粒体氧化磷酸化与磷酸转移中继相结合提供了支持核运输的有效能量单位。
Exchange of information between the nucleus and cytosol depends on the metabolic state of the cell, yet the energy-supply pathways to the nuclear compartment are unknown. Here, the energetics of nucleocytoplasmic communication was determined by imaging import of a constitutive nuclear protein histone H1. Translocation of H1 through nuclear pores in cardiac cells relied on ATP supplied by mitochondrial oxidative phosphorylation, but not by glycolysis. Although mitochondria clustered around the nucleus, reducing the distance for energy transfer, simple nucleotide diffusion was insufficient to meet the energetic demands of nuclear transport. Rather, the integrated phosphotransfer network was required for delivery of high-energy phosphoryls from mitochondria to the nucleus. In neonatal cardiomyocytes with low creatine kinase activity, inhibition of adenylate kinase-catalyzed phosphotransfer abolished nuclear import. With deficient adenylate kinase, nucleoside diphosphate kinase, which secures phosphoryl exchange between ATP and GTP, was unable to sustain nuclear import. Up-regulation of creatine kinase phosphotransfer, to mimic metabolic conditions of adult cardiac cells, rescued H1 import, suggesting a developmental plasticity of the cellular energetic system. Thus, mitochondrial oxidative phosphorylation coupled with phosphotransfer relays provides an efficient energetic unit in support of nuclear transport.