Fatty Acyl Coenzyme A Synthetase Fat1p Regulates Vacuolar Structure and Stationary-Phase Lipophagy in Saccharomyces cerevisiae.
Fatty Acyl Coenzyme A Synthetase Fat1p Regulates Vacuolar Structure and Stationary-Phase Lipophagy in Saccharomyces cerevisiae.
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DOI：
10.1128/spectrum.04625-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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在酵母稳定期，一个单一的球形空泡（溶酶体）是由几个小的融合。此外，液泡膜被重建成两个不同的微区。然而，人们对细胞如何保持空泡形状或调节其微结构域知之甚少。在这里，我们表明，脂肪1 p，脂肪酰辅酶A（酰基辅酶A）合成酶和脂肪酸转运蛋白，而不是合成酶Faa 1 p和Faa 4p，是至关重要的空泡形状的保存，空泡微区的发展，和细胞存活在静止期的酵母酿酒酵母。此外，Fat 1 p对对数期和稳定期细胞中的一般自噬进行负调节。相反，Fat 1 p促进脂肪吞噬，因为FAT 1的缺乏限制了脂滴进入液泡，并减少了液滴（LD）表面蛋白的降解。值得注意的是，补充不饱和脂肪酸或过表达去饱和酶Ole 1 p可以逆转由FAT 1缺乏引起的所有异常表型。我们建议，Fat 1 p调节静止期空泡形态，微区分化，一般自噬，并通过控制膜脂质中的脂肪酸饱和度的脂肪吞噬。重要性感知环境变化和调节细胞代谢水平的能力对细胞活力至关重要。自噬是一个回收利用现有能量资源的过程，而空泡/溶酶体是细胞中最终的自噬加工位点。脂质吞噬是一种选择降解脂滴的自噬过程。在静止期的酵母细胞中，空泡融合并重塑其膜，以产生具有两个不同膜微区的单个球形空泡，这是酵母噬脂作用所需的。在这项研究中，我们发现Fat 1 p能够快速响应营养状态的变化，并通过调节膜脂饱和度来维持酵母S.啤酒。我们的研究结果揭示了细胞如何维持空泡结构和促进空泡表面微区的分化，以实现静止期的脂肪吞噬。
During yeast stationary phase, a single spherical vacuole (lysosome) is created by the fusion of several small ones. Moreover, the vacuolar membrane is reconstructed into two distinct microdomains. Little is known, however, about how cells maintain vacuolar shape or regulate their microdomains. Here, we show that Fat1p, a fatty acyl coenzyme A (acyl-CoA) synthetase and fatty acid transporter, and not the synthetases Faa1p and Faa4p, is essential for vacuolar shape preservation, the development of vacuolar microdomains, and cell survival in stationary phase of the yeast Saccharomyces cerevisiae. Furthermore, Fat1p negatively regulates general autophagy in both log- and stationary-phase cells. In contrast, Fat1p promotes lipophagy, as the absence of FAT1 limits the entry of lipid droplets into the vacuole and reduces the degradation of liquid droplet (LD) surface proteins. Notably, supplementing with unsaturated fatty acids or overexpressing the desaturase Ole1p can reverse all aberrant phenotypes caused by FAT1 deficiency. We propose that Fat1p regulates stationary phase vacuolar morphology, microdomain differentiation, general autophagy, and lipophagy by controlling the degree of fatty acid saturation in membrane lipids. IMPORTANCE The ability to sense environmental changes and adjust the levels of cellular metabolism is critical for cell viability. Autophagy is a recycling process that makes the most of already-existing energy resources, and the vacuole/lysosome is the ultimate autophagic processing site in cells. Lipophagy is an autophagic process to select degrading lipid droplets. In yeast cells in stationary phase, vacuoles fuse and remodel their membranes to create a single spherical vacuole with two distinct membrane microdomains, which are required for yeast lipophagy. In this study, we discovered that Fat1p was capable of rapidly responding to changes in nutritional status and preserving cell survival by regulating membrane lipid saturation to maintain proper vacuolar morphology and the level of lipophagy in the yeast S. cerevisiae. Our findings shed light on how cells maintain vacuolar structure and promote the differentiation of vacuole surface microdomains for stationary-phase lipophagy.
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影响因子：
11.4
作者：
Gopaldass, Navin;Fauvet, Bruno;Mayer, Andreas
通讯作者：
Mayer, Andreas
DOI：
10.1073/pnas.95.15.8625
发表时间：
1998-07-21
影响因子：
11.1
作者：
Hirsch, D;Stahl, A;Lodish, HF
通讯作者：
Lodish, HF
影响因子：
5.5
作者：
Gao Q;Goodman JM
通讯作者：
Goodman JM
影响因子：
3.3
作者：
Adhikari S;Moscatelli J;Puchner EM
通讯作者：
Puchner EM
DOI：
10.1038/s41580-018-0033-y
发表时间：
2018-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Hansen M;Rubinsztein DC;Walker DW
通讯作者：
Walker DW