MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction
MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction
复制标题
DOI：
10.1242/jcs.02645
复制
发表时间：
2005-11-15
影响因子：
4
通讯作者：
Ohta, S
中科院分区：
文献类型：
--
作者：
Nakashima-Kamimura, N;Asoh, S;Ohta, S
为了研究线粒体生物合成中线粒体与细胞核之间相互作用的调控机制，我们发现了一个名为MIDAS（mitochondrial DNA absence sensitive factor）的因子，其表达在线粒体DNA（mitochondrial DNA，mtDNA）缺失时增强。在线粒体疾病患者中，MIDAS表达仅在功能障碍的肌纤维中增加。在HeLa细胞中，大多数MIDAS定位于线粒体，小部分定位于高尔基体。为了研究MIDAS的功能，我们用携带MIDAS cDNA或siRNA的表达载体稳定转染HeLa细胞。组成型表达MIDAS蛋白质和siRNA的细胞分别显示线粒体总质量的增加和减少，伴随着线粒体特异性磷脂心磷脂的调节。相反，线粒体DNA、RNA和蛋白质的量不依赖于MMAS。因此，MIDAS参与线粒体脂质的调节，导致线粒体总质量响应于线粒体功能障碍而增加。
To investigate the regulatory system in mitochondrial biogenesis involving crosstalk between the mitochondria and nucleus, we found a factor named MIDAS (mitochondrial DNA absence sensitive factor) whose expression was enhanced by the absence of mitochondrial DNA (mtDNA). In patients with mitochondrial diseases, MIDAS expression was increased only in dysfunctional muscle fibers. A majority of MIDAS localized to mitochondria with a small fraction in the Golgi apparatus in HeLa cells. To investigate the function of MIDAS, we stably transfected HeLa cells with an expression vector carrying MIDAS cDNA or siRNA. Cells expressing the MIDAS protein and the siRNA constitutively showed an increase and decrease in the total mass of mitochondria, respectively, accompanying the regulation of a mitochondria-specific phospholipid, cardiolipin. In contrast, amounts of the mitochondrial DNA, RNA and proteins did not depend upon MMAS. Thus, MIDAS is involved in the regulation of mitochondrial lipids, leading to increases of total mitochondrial mass in response to mitochondrial dysfunction.