Berberine Induces Mitophagy through Adenosine Monophosphate-Activated Protein Kinase and Ameliorates Mitochondrial Dysfunction in PINK1 Knockout Mouse Embryonic Fibroblasts

Author:

Um Jee-Hyun12,Lee Kang-Min12ORCID,Kim Young-Yeon12,Lee Da-Ye12,Kim Eunmi12,Kim Dong-Hyun34,Yun Jeanho12ORCID

Affiliation:

1. Department of Biochemistry, College of Medicine, Dong-A University, Busan 49201, Republic of Korea

2. Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Republic of Korea

3. Department of Pharmacology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea

4. Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea

Abstract

Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not interfere with mitochondrial function, unlike the well-known mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and subsequently induced mitochondrial biogenesis. Berberine treatment induced the activation of adenosine monophosphate-activated protein kinase (AMPK), and the AMPK inhibitor compound C abolished berberine-induced mitophagy, suggesting that AMPK activation is essential for berberine-induced mitophagy. Notably, berberine treatment reversed mitochondrial dysfunction in PINK1 knockout mouse embryonic fibroblasts. Our results suggest that berberine is a mitophagy-specific inducer and can be used as a therapeutic treatment for neurodegenerative diseases, including Parkinson’s disease, and that natural alkaloids are potential sources of mitophagy inducers.

Funder

Korea Basic Science Institute

Ministry of Health and Welfare

National Research Foundation of Korea

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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