Consiglio Nazionale delle Ricerche Institute of Neuroscience and Department of Biomedical Sciences, University of I-35121 Padova, Italy.
Institute of Molecular Genetics at the Istituto Ortopedico Rizzoli, I-40126 Bologna, Italy.
J Biol Chem. 2011 Dec 2;286(48):41163-41170. doi: 10.1074/jbc.M111.268375. Epub 2011 Oct 7.
We have studied the pathways for Ca(2+) transport in mitochondria of the fruit fly Drosophila melanogaster. We demonstrate the presence of ruthenium red (RR)-sensitive Ca(2+) uptake, of RR-insensitive Ca(2+) release, and of Na(+)-stimulated Ca(2+) release in energized mitochondria, which match well characterized Ca(2+) transport pathways of mammalian mitochondria. Following larger matrix Ca(2+) loading Drosophila mitochondria underwent spontaneous RR-insensitive Ca(2+) release, an event that in mammals is due to opening of the permeability transition pore (PTP). Like the PTP of mammals, Drosophila Ca(2+)-induced Ca(2+) release could be triggered by uncoupler, diamide, and N-ethylmaleimide, indicating the existence of regulatory voltage- and redox-sensitive sites and was inhibited by tetracaine. Unlike PTP-mediated Ca(2+) release in mammals, however, it was (i) insensitive to cyclosporin A, ubiquinone 0, and ADP; (ii) inhibited by P(i), as is the PTP of yeast mitochondria; and (iii) not accompanied by matrix swelling and cytochrome c release even in KCl-based medium. We conclude that Drosophila mitochondria possess a selective Ca(2+) release channel with features intermediate between the PTP of yeast and mammals.
我们研究了果蝇（Drosophila melanogaster）线粒体中的 Ca(2+)转运途径。我们证明了在能量化的线粒体中存在钌红（RR）敏感的 Ca(2+)摄取、RR 不敏感的 Ca(2+)释放以及 Na(+)刺激的 Ca(2+)释放，这与哺乳动物线粒体中特征明确的 Ca(2+)转运途径相匹配。在较大的基质 Ca(2+)负载之后，果蝇线粒体经历自发的 RR 不敏感的 Ca(2+)释放，这种事件在哺乳动物中是由于通透性转换孔（PTP）的开放。与哺乳动物的 PTP 一样，果蝇 Ca(2+)-诱导的 Ca(2+)释放可以被解偶联剂、二酰胺和 N-乙基马来酰亚胺触发，表明存在调节的电压和氧化还原敏感位点，并且被三甲卡因抑制。然而，与哺乳动物的 PTP 介导的 Ca(2+)释放不同，它（i）对环孢菌素 A、泛醌 0 和 ADP 不敏感；（ii）被 Pi 抑制，就像酵母线粒体的 PTP 一样；（iii）即使在基于 KCl 的介质中也不伴随着基质肿胀和细胞色素 c 释放。我们得出结论，果蝇线粒体具有一种选择性的 Ca(2+)释放通道，其特征介于酵母和哺乳动物的 PTP 之间。
