Cooperative function of Fmp30, Mdm31, and Mdm32 in Ups1-independent cardiolipin accumulation in the yeast Saccharomyces cerevisiae.
Cooperative function of Fmp30, Mdm31, and Mdm32 in Ups1-independent cardiolipin accumulation in the yeast Saccharomyces cerevisiae.
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DOI：
10.1038/s41598-017-16661-2
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发表时间：
2017-11-27
影响因子：
4.6
通讯作者：
Kuge O
中科院分区：
文献类型：
--
作者：
Miyata N;Goda N;Matsuo K;Hoketsu T;Kuge O
心磷脂(CL)是由磷脂酸(PA)通过一系列发生在线粒体内膜(MIM)上的酶反应合成的。在酿酒酵母中，UPS1-MDM35介导PA从线粒体外膜(MOM)向MIM的转移。UPS1基因缺失导致细胞内CL水平下降约80%。然而，UPS1∆细胞中CL的积累因UPS2的耗尽而增加，UPS2与MDM35形成蛋白质复合体，并通过PS脱羧酶PSD1介导磷脂酰丝氨酸(PS)从MoM转移到MIM合成磷脂酰乙醇胺(PE)。在本研究中，我们发现，不仅UPS2的缺失，而且编码PS合成酶的PSD1和CHO1的缺失，都会促进UPS1∆细胞中CL的积累，这表明线粒体中低水平的PE与促进UPS1∆细胞中CL的积累有关。此外，UPs1非依赖性和低水平PE促进的CL积累依赖于FMP30、MDM31和MDM32的功能。此外，还揭示了Fmp30与Mdm31和Mdm32之间的物理相互作用。因此，当线粒体PE水平降低时，Fmp30、MDm31和MDm32似乎以不依赖于UPS1的方式协同作用于CL的积累。
Cardiolipin (CL) is synthesized from phosphatidic acid (PA) through a series of enzymatic reactions occurring at the mitochondrial inner membrane (MIM). Ups1-Mdm35 mediates PA transfer from the mitochondrial outer membrane (MOM) to the MIM in the yeast Saccharomyces cerevisiae. Deletion of UPS1 leads to a ~80% decrease in the cellular CL level. However, the CL accumulation in ups1∆ cells is enhanced by the depletion of Ups2, which forms a protein complex with Mdm35 and mediates phosphatidylserine (PS) transfer from the MOM to the MIM for phosphatidylethanolamine (PE) synthesis by a PS decarboxylase, Psd1. In this study, we found that the accumulation of CL in ups1∆ cells was enhanced by deletion of not only UPS2, but also PSD1 and CHO1 encoding a PS synthase, suggesting that low PE levels in mitochondria were relevant to the enhancement of CL accumulation in ups1∆ cells. Furthermore, the Ups1-independent and low-level PE-enhanced CL accumulation was shown to depend on the functions of FMP30, MDM31, and MDM32. In addition, the physical interactions of Fmp30 with Mdm31 and Mdm32 were revealed. Thus, when the mitochondrial PE level is reduced, Fmp30, Mdm31, and Mdm32 seem to function cooperatively for the accumulation of CL in a UPS1-independent manner.
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影响因子：
3.6
作者：
Kuroda, Takuya;Tani, Motohiro;Kuge, Osamu
通讯作者：
Kuge, Osamu
影响因子：
11.4
作者：
Osman, Christof;Haag, Mathias;Langer, Thomas
通讯作者：
Langer, Thomas
MICOS和UPS2-MDM35在线粒体中组织膜脂质合成。
DOI：
10.1083/jcb.201602007
发表时间：
2016-06-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aaltonen MJ;Friedman JR;Osman C;Salin B;di Rago JP;Nunnari J;Langer T;Tatsuta T
通讯作者：
Tatsuta T
影响因子：
7.8
作者：
Dimmer, Kai Stefan;Jakobs, Stefan;Vogel, Frank;Altmann, Katrin;Westermann, Benedikt
通讯作者：
Westermann, Benedikt
影响因子：
29
作者：
Tamura Y;Harada Y;Nishikawa S;Yamano K;Kamiya M;Shiota T;Kuroda T;Kuge O;Sesaki H;Imai K;Tomii K;Endo T
通讯作者：
Endo T