Glycolytic reliance promotes anabolism in photoreceptors

被引:121
作者
Chinchore, Yashodhan [1 ,2 ]
Begaj, Tedi [1 ,2 ]
Wu, David [1 ,2 ]
Drokhlyansky, Eugene [1 ,2 ]
Cepko, Constance L. [1 ,2 ,3 ]
机构
[1] Harvard Med Sch, Dept Genet, Boston, MA 02215 USA
[2] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02215 USA
[3] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02215 USA
来源
ELIFE | 2017年 / 6卷
基金
美国国家卫生研究院;
关键词
FIBROBLAST-GROWTH-FACTOR; PYRUVATE-KINASE M2; LACTATE-DEHYDROGENASE; RETINAL DEGENERATION; AEROBIC GLYCOLYSIS; METABOLIC DIFFERENTIATION; TYROSINE PHOSPHORYLATION; RETINITIS-PIGMENTOSA; MAMMALIAN RETINA; TRANSGENIC MICE;
D O I
10.7554/eLife.25946
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with antagonism of this pathway resulting in anabolic deficits. These data demonstrate the cell autonomous role of the glycolytic pathway in outer segment maintenance and provide evidence that aerobic glycolysis is part of a metabolic program that supports the biosynthetic needs of a normal neuronal cell type.
引用
收藏
页数:22
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