Neuroprotective effects of ATPase inhibitory factor 1 preventing mitochondrial dysfunction in Parkinson's disease

In Hyeok Chung, Han A. Park, Jun Kang, Heyyoung Kim, Su Min Hah, Juhee Lee, Hyeon Soo Kim, Won Seok Choi, Ji Hyung Chung, Min Jeong Shin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Mitochondrial dysfunction is a key element in the progression of Parkinson’s disease (PD). The inefficient operation of the electron transport chain (ETC) impairs energy production and enhances the generation of oxidative stress contributing to the loss of dopaminergic cells in the brain. ATPase inhibitory factor 1 (IF1) is a regulator of mitochondrial energy metabolism. IF1 binds directly to the F1Fo ATP synthase and prevents ATP wasting during compromised energy metabolism. In this study, we found treatment with IF1 protects mitochondria against PD-like insult in vitro. SH-SY5Y cells treated with IF1 were resistant to loss of ATP and mitochondrial inner membrane potential during challenge with rotenone, an inhibitor of complex I in the ETC. We further demonstrated that treatment with IF1 reversed rotenone-induced superoxide production in mitochondria and peroxide accumulation in whole cells. Ultimately, IF1 decreased protein levels of pro-apoptotic Bax, cleaved caspase-3, and cleaved PARP, rescuing SH-SY5Y cells from rotenone-mediated apoptotic death. Administration of IF1 significantly improved the results of pole and hanging tests performed by PD mice expressing human α-synuclein. This indicates that IF1 mitigates PD-associated motor deficit. Together, these findings suggest that IF1 exhibits a neuroprotective effect preventing mitochondrial dysfunction in PD pathology.

Original languageEnglish
Article number3874
JournalScientific reports
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the NRF funded by the Ministry of Science and ICT (NRF-2020R1A2C2005580), and the Ministry of Education (2019R1A2C1004575, WSC).

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General


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