National Creative Research Initiatives Center for Energy Homeostasis Regulation, Seoul National University, Seoul, Korea.
PLoS One. 2010 Oct 7;5(10):e13151. doi: 10.1371/journal.pone.0013151.
Voltage-dependent anion channel (VDAC) has been suggested to be a mediator of mitochondrial-dependent cell death induced by Ca(2+) overload, oxidative stress and Bax-Bid activation. To confirm this hypothesis in vivo, we generated and characterized Drosophila VDAC (porin) mutants and found that Porin is not required for mitochondrial apoptosis, which is consistent with the previous mouse studies. We also reported a novel physiological role of Porin. Loss of porin resulted in locomotive defects and male sterility. Intriguingly, porin mutants exhibited elongated mitochondria in indirect flight muscle, whereas Porin overexpression produced fragmented mitochondria. Through genetic analysis with the components of mitochondrial fission and fusion, we found that the elongated mitochondria phenotype in porin mutants were suppressed by increased mitochondrial fission, but enhanced by increased mitochondrial fusion. Furthermore, increased mitochondrial fission by Drp1 expression suppressed the flight defects in the porin mutants. Collectively, our study showed that loss of Drosophila Porin results in mitochondrial morphological defects and suggested that the defective mitochondrial function by Porin deficiency affects the mitochondrial remodeling process.
电压依赖性阴离子通道（VDAC）被认为是 Ca（2+）超载、氧化应激和 Bax-Bid 激活诱导的线粒体依赖性细胞死亡的介质。为了在体内证实这一假说，我们生成并表征了果蝇 VDAC（孔蛋白）突变体，并发现 Porin 对于线粒体凋亡不是必需的，这与之前的小鼠研究一致。我们还报道了 Porin 的一个新的生理作用。Porin 的缺失导致运动缺陷和雄性不育。有趣的是，Porin 突变体的间接飞行肌中出现线粒体伸长，而 Porin 过表达则产生线粒体碎片化。通过与线粒体分裂和融合组件的遗传分析，我们发现 Porin 突变体中伸长的线粒体表型被增加的线粒体分裂所抑制，但被增加的线粒体融合所增强。此外，通过 Drp1 表达增加线粒体分裂抑制了 Porin 突变体的飞行缺陷。总之，我们的研究表明，果蝇 Porin 的缺失导致线粒体形态缺陷，并表明 Porin 缺乏导致的线粒体功能缺陷影响线粒体重塑过程。
