Rikhy R, Kamat S, Ramagiri S, Sriram V, Krishnan K S
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, India.
Genes Brain Behav. 2007 Feb;6(1):42-53. doi: 10.1111/j.1601-183X.2006.00218.x.
Mitochondria are the primary source of ATP needed for the steps of the synaptic vesicle cycle. Dynamin-related protein (DRP) is involved in the fission of mitochondria and peroxisomes. To assess the role of mitochondria in synaptic function, we characterized a Drosophila DRP mutant combination that shows an acute temperature-sensitive paralysis. Sequencing of the mutant reveals a single amino acid change in the guanosine triphosphate hydrolysing domain (GTPase domain) of DRP. The synaptic mitochondria in these mutants are remarkably elongated, suggesting a role for DRP in mitochondrial fission in Drosophila. There is a loss of neuronal transmission at restrictive temperatures in electroretinogram (ERG) recordings. Like stress-sensitive B (sesB), a mitochondrial adenosine triphosphate (ATP) translocase mutant we studied earlier for its effects on synaptic vesicle recycling, an allele-specific reduction in the temperature of paralysis of Drosophila synaptic vesicle recycling mutant shibire was seen in the DRP mutant background. These data, in addition to depletion of vesicles observed in electron microscopic sections of photoreceptor synapses at restrictive temperatures, suggest a block in synaptic vesicle recycling due to reduced mitochondrial function.
线粒体是突触小泡循环各步骤所需ATP的主要来源。动力相关蛋白(DRP)参与线粒体和过氧化物酶体的分裂。为了评估线粒体在突触功能中的作用,我们对一种表现出急性温度敏感性麻痹的果蝇DRP突变体组合进行了表征。对该突变体的测序显示,DRP的鸟苷三磷酸水解结构域(GTPase结构域)中有一个氨基酸发生了变化。这些突变体中的突触线粒体显著延长,表明DRP在果蝇线粒体分裂中发挥作用。在视网膜电图(ERG)记录中,在限制温度下神经元传递丧失。就像应激敏感B(sesB)一样,我们之前研究过的一种线粒体腺苷三磷酸(ATP)转位酶突变体,它对突触小泡循环有影响,在DRP突变体背景中,果蝇突触小泡循环突变体shibire的麻痹温度出现了等位基因特异性降低。这些数据,除了在限制温度下在光感受器突触的电子显微镜切片中观察到小泡耗竭外,还表明由于线粒体功能降低导致突触小泡循环受阻。