The mitochondrial network structure dynamically adapts to cellular metabolic challenges. Mitochondrial depolarisation, particularly, induces fragmentation of the network. This fragmentation may be a result of either a direct regulation of the mitochondrial fusion machinery by transmembrane potential or an indirect effect of metabolic remodelling. Activities of ATP synthase and adenine nucleotide translocator (ANT) link the mitochondrial transmembrane potential with the cytosolic NTP/NDP ratio. Given that mitochondrial fusion requires cytosolic GTP, a decrease in the NTP/NDP ratio might also account for protonophore-induced mitochondrial fragmentation. For evaluating the contributions of direct and indirect mechanisms to mitochondrial remodelling, we assessed the morphology of the mitochondrial network in yeast cells with inhibited ANT. We showed that the repression of AAC2 (PET9), a major ANT gene in yeast, increases mitochondrial transmembrane potential. However, the mitochondrial network in this strain was fragmented. Meanwhile, AAC2 repression did not prevent mitochondrial fusion in zygotes; nor did it inhibit mitochondrial hyperfusion induced by Dnm1p inhibitor mdivi-1. These results suggest that the inhibition of ANT, rather than preventing mitochondrial fusion, facilitates mitochondrial fission. The protonophores were not able to induce additional mitochondrial fragmentation in an AAC2-repressed strain and in yeast cells with inhibited ATP synthase. Importantly, treatment with the ATP synthase inhibitor oligomycin A also induced mitochondrial fragmentation and hyperpolarization. Taken together, our data suggest that ATP/ADP translocation plays a crucial role in shaping of the mitochondrial network and exemplify that an increase in mitochondrial membrane potential does not necessarily oppose mitochondrial fragmentation.

中文翻译：

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带有抑制的腺嘌呤核苷酸转运蛋白AAC2的酵母中的线粒体动力学。

线粒体网络结构动态适应细胞代谢挑战。线粒体去极化尤其会诱导网络分裂。这种分裂可能是由于跨膜电位直接调节线粒体融合机制或代谢重塑的间接作用所致。ATP合酶和腺嘌呤核苷酸转运蛋白（ANT）的活性将线粒体跨膜电位与胞质NTP / NDP比值联系起来。考虑到线粒体融合需要胞质GTP，NTP / NDP比值的降低也可能是质子体诱导的线粒体片段化的原因。为了评估直接和间接机制对线粒体重塑的贡献，我们评估了具有受抑制的ANT的酵母细胞中线粒体网络的形态。我们表明，AAC2（PET9），酵母中的主要ANT基因的阻遏增加线粒体跨膜的潜力。但是，该菌株中的线粒体网络是碎片化的。同时，抑制AAC2不能阻止受精卵中的线粒体融合。它也没有抑制Dnm1p抑制剂mdivi-1诱导的线粒体过度融合。这些结果表明，抑制ANT而不是阻止线粒体融合，促进了线粒体裂变。质子体无法在AAC2抑制的菌株中以及在具有抑制的ATP合酶的酵母细胞中诱导额外的线粒体片段化。重要的是，用ATP合酶抑制剂寡霉素A的治疗还诱导线粒体断裂和超极化。在一起