Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover
Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover
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DOI：
10.1093/jb/mvy057
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发表时间：
2018-11-01
影响因子：
2.7
通讯作者：
Esaki, Masatoshi
中科院分区：
文献类型：
--
作者：
Chowdhury, Abhijit;Ogura, Teru;Esaki, Masatoshi
线粒体在营养生长过程中不断进行协调的融合和裂变，以保持其同质性并去除受损的成分。胞质 AAA ATP 酶 Cdc48 参与线粒体融合事件和线粒体外膜中负责融合的 GTP 酶 Fzo1 的周转，表明线粒体融合和 Fzo1 周转之间可能存在联系。在这里，我们鉴定了两种涉及线粒体调节的 Cdc48 辅因子蛋白 Ubp3 和 Ubx2。在没有 UBP3 的情况下，观察到线粒体断裂和聚集。 Fzo1 的转换在 ubp3 中没有受到影响，而是稳定了从 Fzo1 中去除融合所需的多聚泛素链的去泛素化酶 Ubp12。因此，过量的 Ubp12 可能会通过去除具有融合能力的泛素化 Fzo1 来导致线粒体断裂。相反，UBX2 的删除会扰乱 Fzo1 寡聚体的解体及其降解，但不会改变线粒体形态。UBX2缺失导致 Ubp2 不稳定，通过去除降解信号多聚泛素链来负向调节 Fzo1 周转，表明 Ubx2 将直接促进 Fzo1 降解。这些结果表明，两种不同的 Cdc48-辅因子复合物独立调节线粒体融合和 Fzo1 周转。
Mitochondria continuously undergo coordinated fusion and fission during vegetative growth to keep their homogeneity and to remove damaged components. A cytosolic AAA ATPase, Cdc48, is implicated in the mitochondrial fusion event and turnover of a fusion-responsible GTPase in the mitochondrial outer membrane, Fzo1, suggesting a possible linkage of mitochondrial fusion and Fzo1 turnover. Here, we identified two Cdc48 cofactor proteins, Ubp3 and Ubx2, involving mitochondria regulation. In the absence of UBP3, mitochondrial fragmentation and aggregation were observed. The turnover of Fzo1 was not affected in " ubp3, but instead a deubiquitylase Ubp12 that removes fusion-required polyubiquitin chains from Fzo1 was stabilized. Thus, excess amount of Ubp12 may lead to mitochondrial fragmentation by removal of fusion-competent ubiquitylated Fzo1. In contrast, deletion of UBX2 perturbed disassembly of Fzo1 oligomers and their degradation without alteration of mitochondrial morphology. The UBX2 deletion led to destabilization of Ubp2 that negatively regulates Fzo1 turnover by removing degradation-signalling polyubiquitin chains, suggesting that Ubx2 would directly facilitate Fzo1 degradation. These results indicated that two different Cdc48-cofactor complexes independently regulate mitochondrial fusion and Fzo1 turnover.