Impaired phosphatidylethanolamine metabolism activates a reversible stress response that detects and resolves mutant mitochondrial precursors.
Impaired phosphatidylethanolamine metabolism activates a reversible stress response that detects and resolves mutant mitochondrial precursors.
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DOI：
10.1016/j.isci.2021.102196
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发表时间：
2021-03-19
期刊：
影响因子：
5.8
通讯作者：
Claypool SM
中科院分区：
文献类型：
--
作者：
Sam PN;Calzada E;Acoba MG;Zhao T;Watanabe Y;Nejatfard A;Trinidad JC;Shutt TE;Neal SE;Claypool SM
磷脂酰乙醇胺（PE）在线粒体中产生，长期以来一直被认为是一个重要的前体磷脂酰胆碱的生产，发生在内质网（ER）。最近，严格的线粒体定位的酶，使PE在磷脂酰丝氨酸脱羧酶1（Psd 1），受到质疑。由于Psd 1在ER的双重定位具有深远的意义，我们开始了我们的研究，以独立地重新评估Psd 1的亚细胞分布。我们的研究结果支持了一个不可避免的结论，即绝大多数，如果不是全部，功能Psd 1驻留在cardion。通过我们的努力，我们发现，Psd 1的突变形式，损害自我加工步骤需要它成为功能性的双重定位到ER时，在PE限制的环境中表达。我们的结论是，严重受损的细胞PE代谢会引发ER辅助的适应性反应，该反应能够识别和解决无功能的线粒体前体。功能性Psd 1是制造PE的酶，位于线粒体中。当细胞PE代谢受损时，突变型Psd 1也靶向ER。靶向ER的突变型Psd 1被泛素化并迅速降解。PE代谢受损会激活可逆的应激反应分子生理学;细胞生物学;蛋白质组学
Phosphatidylethanolamine (PE) made in mitochondria has long been recognized as an important precursor for phosphatidylcholine production that occurs in the endoplasmic reticulum (ER). Recently, the strict mitochondrial localization of the enzyme that makes PE in the mitochondrion, phosphatidylserine decarboxylase 1 (Psd1), was questioned. Since a dual localization of Psd1 to the ER would have far-reaching implications, we initiated our study to independently re-assess the subcellular distribution of Psd1. Our results support the unavoidable conclusion that the vast majority, if not all, of functional Psd1 resides in the mitochondrion. Through our efforts, we discovered that mutant forms of Psd1 that impair a self-processing step needed for it to become functional are dually localized to the ER when expressed in a PE-limiting environment. We conclude that severely impaired cellular PE metabolism provokes an ER-assisted adaptive response that is capable of identifying and resolving nonfunctional mitochondrial precursors. Functional Psd1, the enzyme that makes PE, is mitochondrial localized When cellular PE metabolism is impaired, mutant Psd1 is also targeted to the ER Mutant Psd1 targeted to the ER is ubiquitinated and rapidly degraded Impaired PE metabolism activates a reversible stress response Molecular Physiology; Cell Biology; Proteomics
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影响因子：
3.3
作者：
Birner, R;Bürgermeister, M;Daum, G
通讯作者：
Daum, G
DOI：
10.1016/j.bbalip.2004.09.007
发表时间：
2004-11-08
影响因子：
4.8
作者：
Bürgermeister, M;Birner-Grünberger, R;Daum, G
通讯作者：
Daum, G
影响因子：
3.9
作者：
Girisha, Katta M.;von Elsner, Leonie;Mortier, Geert
通讯作者：
Mortier, Geert
影响因子：
3.3
作者：
Baile MG;Whited K;Claypool SM
通讯作者：
Claypool SM
DOI：
10.1083/jcb.201008177
发表时间：
2011-02-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Claypool SM;Whited K;Srijumnong S;Han X;Koehler CM
通讯作者：
Koehler CM