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Rat liver GTP-binding proteins mediate changes in mitochondrial membrane potential and organelle fusion.

机译:大鼠肝脏GTP结合蛋白介导线粒体膜电位和细胞器融合的变化。

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摘要

The variety of mitochondrial morphology in healthy and diseased cells can be explained by regulated mitochondrial fusion. Previously, a mitochondrial outer membrane fraction containing fusogenic, aluminum fluoride (AlF4)-sensitive GTP-binding proteins (mtg) was separated from rat liver (J. D. Cortese, Exp. Cell Res. 240: 122-133, 1998). Quantitative confocal microscopy now reveals that mtg transiently increases mitochondrial membrane potential (DeltaPsi) when added to permeabilized rat hepatocytes (15%), rat fibroblasts (19%), and rabbit myocytes (10%). This large mtg-induced DeltaPsi increment is blocked by fusogenic GTPase-specific modulators such as guanosine 5'-O-(3-thiotriphosphate), excess GTP (>100 microM), and AlF4, suggesting a linkage between DeltaPsi and mitochondrial fusion. Accordingly, stereometric analysis shows that decreasing DeltaPsi or ATP synthesis with respiratory inhibitors limits mtg- and AlF4-induced mitochondrial fusion. Also, a specific G protein inhibitor (Bordetella pertussis toxin) hyperpolarizes mitochondria and leads to a loss of AlF4-dependent mitochondrial fusion. These results place mtg-induced DeltaPsi changes upstream of AlF4-induced mitochondrial fusion, suggesting that GTPases exert DeltaPsi-dependent control of the fusion process. Mammalian mitochondrial morphology thus can be modulated by cellular energetics.
机译:健康和患病细胞中线粒体形态的多样性可以通过调节的线粒体融合来解释。以前,从大鼠肝脏中分离出含有融合的氟化铝(AlF4)敏感的GTP结合蛋白(mtg)的线粒体外膜部分(J. D. Cortese,Exp。Cell Res。240:122-133,1998)。定量共聚焦显微镜现在显示,当将mtg加入到透化的大鼠肝细胞(15%),大鼠成纤维细胞(19%)和兔心肌细胞(10%)中时,其线粒体膜电位(DeltaPsi)会瞬时增加。大量的mtg诱导的DeltaPsi增量被融合GTPase特异性调节剂(如鸟苷5'-O-(3-硫代三磷酸),过量的GTP(> 100 microM)和AlF4)阻滞,表明DeltaPsi和线粒体融合之间存在联系。因此,立体分析表明,使用呼吸抑制剂降低DeltaPsi或ATP合成会限制mtg-和AlF4诱导的线粒体融合。此外,一种特定的G蛋白抑制剂(百日咳杆菌毒素)会使线粒体超极化,并导致依赖AlF4的线粒体融合丧失。这些结果将mtg诱导的DeltaPsi变化置于AlF4诱导的线粒体融合的上游,表明GTPases对融合过程施加了DeltaPsi依赖性控制。因此,哺乳动物的线粒体形态可以通过细胞能量学来调节。

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