Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy.
Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy.
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DOI：
10.1016/j.cellsig.2016.06.015
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发表时间：
2016-09
影响因子：
4.8
通讯作者：
Ketteler R
中科院分区：
文献类型：
--
作者：
Heintze J;Costa JR;Weber M;Ketteler R
自噬和细胞代谢是紧密相连的过程，但个体代谢酶如何调节自噬过程尚不清楚。这项研究表明 5-磷酸核糖异构酶 (RPIA)（戊糖磷酸途径的关键调节因子）参与自噬的控制。我们使用双基因删除策略，将 shRNA 介导的敲低研究与 CRISPR/Cas9 基因组编辑相结合。通过 shRNA 敲低 RPIA 或通过 CRISPR/Cas9 基因组编辑删除基因组，会导致 ATG4B 介导的 LC3 加工增加，并导致细胞中出现 LC3 阳性自噬体。敲低 RPIA 后 LC3 加工的增加可以通过抗氧化剂 N-乙酰半胱氨酸的治疗来逆转。结果与 RPIA 通过调节氧化还原信号传导抑制自噬和 LC3 加工的模型一致。 5-磷酸核糖异构酶将自噬与磷酸戊糖途径联系起来。生成 CRISPR/Cas9 基因组编辑的 RPIA 敲除细胞系 RPIA 异构酶抑制细胞 LC3 加工和自噬体形成。
Autophagy and cellular metabolism are tightly linked processes, but how individual metabolic enzymes regulate the process of autophagy is not well understood. This study implicates ribose-5-phosphate isomerase (RPIA), a key regulator of the pentose phosphate pathway, in the control of autophagy. We used a dual gene deletion strategy, combining shRNA-mediated knockdown studies with CRISPR/Cas9 genome editing. Knockdown of RPIA by shRNA or genomic deletion by CRISPR/Cas9 genome editing, results in an increase of ATG4B-mediated LC3 processing and in the appearance of LC3-positive autophagosomes in cells. Increased LC3 processing upon knockdown of RPIA can be reversed by treatment with the antioxidant N-acetyl cysteine. The results are consistent with a model in which RPIA suppresses autophagy and LC3 processing by modulation of redox signaling. Ribose-5-phosphate isomerase links autophagy with the pentose phosphate pathway. Generation of a CRISPR/Cas9 genome edited RPIA knockout cell line RPIA isomerase suppresses cellular LC3 processing and autophagosome formation.
影响因子：
3.1
作者：
Ketteler R;Tomov V;Neunkirchner A;Xie Q;Pickl WF;Seed B
通讯作者：
Seed B