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《通过整合亚细胞和全细胞蛋白质组分析揭示枝顶孢霉衰老过程中的脂滴作用》

The Role of Lipid Droplets in Mortierella alpina Aging Revealed by Integrative Subcellular and Whole-Cell Proteome Analysis.

机构信息

Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, 211800, China.

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211800, China.

出版信息

Sci Rep. 2017 Mar 7;7:43896. doi: 10.1038/srep43896.

Abstract

Lipid droplets (LDs) participate in many cellular processes in oleaginous microorganisms. However, the exact function of LDs in the Mortierella alpina aging process remains elusive. Herein, subcellular proteomics was employed to unveil the composition and dynamics of the LD proteome in the aging M. alpina for the first time. More than 400 proteins were detected in LDs and 62 of them changed expression significantly during aging. By combining the LD proteomic data with whole-cell data, we found that the carbohydrate metabolism and de novo lipid biosynthesis were all inhibited during aging of M. alpina mycelia. The up-regulation of fructose metabolism-related enzymes in LDs might imply that LDs facilitated the fructose metabolism, which in turn might cause pyruvate to accumulate and enter malate-pyruvate cycle, and ultimately, provide additional NADPH for the synthesis of arachidonic acid (ARA). Lysophospholipase and lecithinase were up-regulated in LDs during the aging process, suggesting that the phospholipids and lecithin were starting to be hydrolyzed, in order to release fatty acids for the cells. The impairment of the anti-oxidant system might lead to the accumulation of ROS and consequently cause the up-regulation of autophagy-related proteins in LDs, which further induces the M. alpina mycelia to activate the autophagy process.

摘要

脂滴 (LDs) 参与了油脂微生物的许多细胞过程。然而,LDs 在高山被孢霉老化过程中的确切功能仍不清楚。在此,首次采用亚细胞蛋白质组学技术揭示了高山被孢霉老化过程中 LD 蛋白质组的组成和动态。在 LDs 中检测到超过 400 种蛋白质,其中 62 种在老化过程中表达显著变化。将 LD 蛋白质组学数据与全细胞数据相结合,我们发现高山被孢霉菌丝体老化过程中碳水化合物代谢和从头脂质生物合成均受到抑制。LDs 中果糖代谢相关酶的上调可能暗示 LDs 促进了果糖代谢,进而导致丙酮酸积累并进入苹果酸-丙酮酸循环,最终为花生四烯酸 (ARA) 的合成提供额外的 NADPH。在老化过程中,LDs 中的溶血磷脂酶和卵磷脂酶上调,表明磷脂和卵磷脂开始水解,以释放脂肪酸供细胞使用。抗氧化系统的损伤可能导致 ROS 积累,从而导致 LDs 中自噬相关蛋白的上调,进而诱导高山被孢霉菌丝体激活自噬过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d315/5339828/de1ae3e9ef32/srep43896-f1.jpg

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