Phosphatidylethanolamine positively regulates autophagy and longevity

被引:203
作者
Rockenfeller, P. [1 ]
Koska, M. [1 ]
Pietrocola, F. [2 ]
Minois, N. [3 ]
Knittelfelder, O. [1 ]
Sica, V. [2 ]
Franz, J. [1 ]
Carmona-Gutierrez, D. [1 ]
Kroemer, G. [2 ,4 ,5 ,6 ,7 ]
Madeo, F. [1 ,8 ]
机构
[1] Graz Univ, Inst Mol Biosci, NAWI Graz, A-8010 Graz, Austria
[2] INSERM, U848, Paris, France
[3] Univ St Andrews, St Andrews, Fife, Scotland
[4] Inst Gustave Roussy, Villejuif, France
[5] Ctr Rech Cordeliers, Paris, France
[6] Hop Europeen Georges Pompidou, AP HP, Paris, France
[7] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[8] BioTechMed Graz, A-8010 Graz, Austria
基金
欧洲研究理事会; 奥地利科学基金会;
关键词
YEAST SACCHAROMYCES-CEREVISIAE; LIPID DROPLET FORMATION; PHOSPHATIDYLSERINE DECARBOXYLASE; SUBCELLULAR MEMBRANES; MONITORING AUTOPHAGY; PROTEIN LIPIDATION; DIFFERENT PATHWAYS; MAMMALIAN-CELLS; LIFE-SPAN; GENE;
D O I
10.1038/cdd.2014.219
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death. Conversely, the artificial increase of intracellular PE levels, by provision of its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1, significantly increased autophagic flux, both in yeast and in mammalian cell culture. Importantly administration of ethanolamine was sufficient to extend the lifespan of yeast (Saccharomyces cerevisiae), mammalian cells (U2OS, H4) and flies (Drosophila melanogaster). We thus postulate that the availability of PE may constitute a bottleneck for functional autophagy and that organismal life or healthspan could be positively influenced by the consumption of ethanolamine-rich food.
引用
收藏
页码:499 / 508
页数:10
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