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

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...

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Published in:International journal of molecular sciences 2023-12, Vol.25 (1), p.219
Main Authors: Um, Jee-Hyun, Lee, Kang-Min, Kim, Young-Yeon, Lee, Da-Ye, Kim, Eunmi, Kim, Dong-Hyun, Yun, Jeanho
Format: Article
Language:English
Subjects:
Adenosine
Adenylic acid
AMP-Activated Protein Kinases
Animals
B cells
Berberine - pharmacology
Biosynthesis
Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology
Cell death
Fibroblasts
Health aspects
Humans
Kinases
Mice
Mice, Knockout
Microscopy
Mitochondria
Mitochondrial Diseases
Mitophagy
Nervous system diseases
Parkinson Disease
Parkinson's disease
Phosphorylation
Protein kinases
Proteins
Scientific equipment and supplies industry
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25010219