Journal of Biological Chemistry
Volume 287, Issue 9, 24 February 2012, Pages 6628-6641
Journal home page for Journal of Biological Chemistry

Molecular Bases of Disease
Glutathione S-Transferase Omega 1 Activity Is Sufficient to Suppress Neurodegeneration in a Drosophila Model of Parkinson Disease*

https://doi.org/10.1074/jbc.M111.291179Get rights and content
Under a Creative Commons license
open access

A loss-of-function mutation in the gene parkin causes a common neurodegenerative disease that may be caused by mitochondrial dysfunction. Glutathione S-transferase Omega (GSTO) is involved in cell defense mechanisms, but little is known about the role of GSTO in the progression of Parkinson disease. Here, we report that restoration of Drosophila GSTO1 (DmGSTO1), which is down-regulated in parkin mutants, alleviates some of the parkin pathogenic phenotypes and that the loss of DmGSTO1 function enhances parkin mutant phenotypes. We further identified the ATP synthase β subunit as a novel in vivo target of DmGSTO1. We found that glutathionylation of the ATP synthase β subunit is rescued by DmGSTO1 and that the expression of DmGSTO1 partially restores the activity and assembly of the mitochondrial F1F0-ATP synthase in parkin mutants. Our results suggest a novel mechanism for the protective role of DmGSTO1 in parkin mutants, through the regulation of ATP synthase activity, and provide insight into potential therapies for Parkinson disease neurodegeneration.

ATP Synthase
Drosophila Genetics
Enzymes
Mitochondria
Parkinson Disease
Glutathione S-Transferase

Cited by (0)

Author's Choice—Final version full access.

*

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by Ministry of Education, Science, and Technology (MEST) Grants KRF-2008-313-E00068 and 2011-0004860 and by Brain Korea 21 Research Fellowships from the Ministry of Education, Science, and Technology of Korea.

This article contains supplemental Figs. S1–S7.

1

Present address: Dept. of Neurology, Washington University School of Medicine, St. Louis, MO 63110.