PDI-mediated S-nitrosylation of DRP1 facilitates DRP1-S616 phosphorylation and mitochondrial fission in CA1 neurons

Cell Death & Disease
Duk-Shin Lee, Ji-Eun Kim

Abstract

Dynamin-related protein 1 (DRP1) is a key molecule to regulate mitochondrial fission. DRP1 activity is modulated by phosphorylation and S-nitrosylation on serine and cysteine residues, respectively. However, it is still unexplored whether S-nitrosylation of DRP1 affects its phosphorylation. In the present study, we found that Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a NOS inhibitor) abolished S-nitrosylated (SNO-DRP1) and DRP1-serine (S) 616 phosphorylation levels in CA1 neurons under physiological condition. L-NAME led to mitochondrial elongation. In spite of the sustained NO synthesis, status epilepticus (a prolonged seizure activity, SE) diminished SNO-DRP1 and DRP1-S616 levels in CA1 neurons, accompanied by the reduced protein disulfide isomerase (PDI) expression and mitochondrial elongation. SE did not influence thioredoxin 1 (Trx1, a denitrosylating enzyme) activity, which was unaffected by L-NAME under physiological and post-SE condition. PDI knockdown decreased SNO-DRP1 and DRP1-S616 levels concomitant with mitochondrial elongation in CA1 neurons without altered NO synthesis under physiological condition. These findings indicate that PDI may be a NO donor of DRP1 to regulate DRP1-S616 phosphorylation, ind...Continue Reading

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Citations

Jan 15, 2020·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Nov 12, 2018·Cellular and Molecular Life Sciences : CMLS·Dario C Altieri
Jul 28, 2020·Neuronal Signaling·Richard SeagerKevin A Wilkinson
Dec 20, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Liliana Rojas-CharryMichael J Schmeisser
Mar 23, 2021·Journal of Biochemical and Molecular Toxicology·Li-Ting ChenDan-Yan Zhu
May 31, 2021·Free Radical Biology & Medicine·Lixi ShiShengbin Huang
Jul 6, 2021·Free Radical Biology & Medicine·Tomohiro NakamuraStuart A Lipton
Jun 14, 2019·Experimental Cell Research·Xiaoling ZhangXiaoqun Ge

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Methods Mentioned

BETA
protein folding
co-immunoprecipitation
GTPase
protein assay

Software Mentioned

LabChart Pro
ZEN lite
ImageQuant

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