Frataxin activates mitochondrial energy conversion and oxidative phosphorylation
Frataxin activates mitochondrial energy conversion and oxidative phosphorylation
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DOI：
10.1073/pnas.220403797
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发表时间：
2000-10-24
影响因子：
11.1
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Ristow, M;Pfister, MF;Kahn, CR
弗里德赖希共济失调（Friedreich's ataxia，FA）是一种由线粒体共济失调蛋白（frataxin）表达降低引起的常染色体隐性遗传病，其生物学功能尚不清楚。在酵母中的共济失调蛋白的同源物YFH 1是细胞呼吸所需的，并被认为调节线粒体铁稳态。患有FA的患者在骨骼肌中表现出ATP产生减少。我们现在证明，在哺乳动物细胞中过表达共济失调蛋白导致Ca 2+诱导的三羧酸循环通量和呼吸的上调，这反过来又导致线粒体膜电位（Delta Psim）增加，并导致细胞ATP含量升高。因此，共济失调蛋白似乎是线粒体能量转换和氧化磷酸化的关键激活剂。
lFriedreich's ataxia (FA) is an autosomal recessive disease caused by decreased expression of the mitochondrial protein frataxin, The biological function of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is required for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients suffering from FA exhibit decreased ATP production in skeletal muscle, We now demonstrate that overexpression of frataxin in mammalian cells causes a Ca2+-induced up-regulation of tricarboxylic acid cycle flux and respiration, which, in turn, leads to an increased mitochondrial membrane potential (Delta Psim) and results in an elevated cellular ATP content. Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation.