Cyclophilin 1 (Cyp1) mutation ameliorates oxidative stress-induced defects in a Drosophila DJ-1 null mutant

Journal Article · Thu Nov 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.10.014· OSTI ID:23134107

Kim, Eun Young; Kang, Kyong-hwa; Koh, Hyongjong ^[1]

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1. Department of Pharmacology, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, South (Korea, Republic of)

Highlights: • Drosophila Cyp1 mutant exhibits no significant defects in mitochondria. • Cyp1 mutant shows decreased lipid peroxidation. • Cyp1 inhibition increases fly survival under oxidative stress. • Cyp1 mutation ameliorates oxidative stress-induced defects in a DJ-1 mutant model. Drosophila cyclophilin 1 (Cyp1) is a structural and functional homolog of mammalian cyclophilin D (CypD), a unique mitochondrial cyclophilin (Cyp) that regulates the inner mitochondrial membrane permeability transition and cell survival under cellular stresses such as oxidative damage. In this study, we generated and characterized a Drosophila Cyp1 mutant. Cyp1 mutant flies successfully developed into adults and showed no significant defects in mitochondrial morphology, function, and content. However, oxidative damage significantly decreased in Cyp1 mutant flies, and inhibition of Cyp1 expression substantially increased the survival under various oxidative stress paradigms. Moreover, Cyp1 mutation successfully ameliorated survival rates, locomotor activity, and dopaminergic neuron quantity in a Drosophila DJ-1 mutant under oxidative stress, further confirming the protective role of Cyp1 mutation against oxidative stress. In conclusion, these results suggest Cyp1 and its human homolog CypD as putative molecular targets for the treatment of DJ-1 deficiency-associated diseases, including Parkinson's disease.

• OSTI ID: 23134107
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 505; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DROSOPHILA
MITOCHONDRIA
NERVE CELLS
OXIDATION