Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether
Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether
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关键的重新鉴定证实Mitofusin 2是内质网-线粒体系绳
DOI：
10.1073/pnas.1606786113
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发表时间：
2016-10-04
影响因子：
11.1
通讯作者：
Scorrano, Luca
中科院分区：
文献类型：
--
作者：
Naon, Deborah;Zaninello, Marta;Scorrano, Luca
线粒体-内质网（ER）并列在细胞生物学中的多重作用的发现通常依赖于线粒体融合蛋白（Mfn）2作为ER-线粒体系链的开发。然而，这种已建立的Mfn 2功能最近受到质疑，要求重新评估Mfn 2在ER-线粒体串扰中的作用。电子显微镜和荧光探针的细胞器接近证实，ER-线粒体并列减少组成或急性Mfn 2缺失。在功能上，线粒体摄取的钙释放的ER减少急性Mfn 2消融后，以及在Mfn 2（-/-）细胞过表达线粒体钙单向转运蛋白。在分离的Mfn 2（-/-）肝脏线粒体中，线粒体Ca 2+摄取率和程度正常，这与急性或慢性Mfn 2消融或过表达不会改变线粒体钙单向转运体复合物组分水平的发现一致。因此，Mfn 2作为一个真正的ER-线粒体系链，其消融减少了细胞器间的并列和通信。
The discovery of the multiple roles of mitochondria-endoplasmic reticulum (ER) juxtaposition in cell biology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether. However, this established Mfn2 function was recently questioned, calling for a critical re-evaluation of Mfn2's role in ER-mitochondria cross-talk. Electron microscopy and fluorescence-based probes of organelle proximity confirmed that ER-mitochondria juxtaposition was reduced by constitutive or acute Mfn2 deletion. Functionally, mitochondrial uptake of Ca2+ released from the ER was reduced following acute Mfn2 ablation, as well as in Mfn2(-/-) cells overexpressing the mitochondrial calcium uniporter. Mitochondrial Ca2+ uptake rate and extent were normal in isolated Mfn2(-/-) liver mitochondria, consistent with the finding that acute or chronic Mfn2 ablation or overexpression did not alter mitochondrial calcium uniporter complex component levels. Hence, Mfn2 stands as a bona fide ER-mitochondria tether whose ablation decreases interorganellar juxtaposition and communication.