miR-124 coordinates metabolic regulators acting at early stages of human neurogenesis
Metabolic dysregulation of neurons is associated with diverse human brain disorders. Metabolic reprogramming occurs during neuronal differentiation, but it is not fully understood which molecules regulate metabolic changes at the early stages of neurogenesis. In this study, we report that miR-124 is a driver of metabolic change at the initiating stage of human neurogenesis. Proteome analysis has shown the oxidative phosphorylation pathway to be the most significantly altered among the differentially expressed proteins (DEPs) in the immature neurons after the knockdown of miR-124. In agreement with these proteomics results, miR-124-depleted neurons display mitochondrial dysfunctions, such as decreased mitochondrial membrane potential and cellular respiration. Moreover, morphological analyses of mitochondria in early differentiated neurons after miR-124 knockdown result in smaller and less mature shapes. Lastly, we show the potential of identified DEPs as novel metabolic regulators in early neuronal development by validating the effects of GSTK1 on cellular respiration. GSTK1, which is upregulated most significantly in miR-124 knockdown neurons, reduces the oxygen consumption rate of neural cells. Collectively, our data highlight the roles of miR-124 in coordinating metabolic maturation at the early stages of neurogenesis and provide insights into potential metabolic regulators associated with human brain disorders characterized by metabolic dysfunctions.
Authors
- Ji-Hoon Son (ORCID: https://orcid.org/0000-0003-3233-039X)
- Apuã C.M. Paquola (ORCID: https://orcid.org/0000-0002-1329-6870)
- Junho K. Hur (ORCID: https://orcid.org/0000-0003-3794-1149)
- Gyung Whan Kim (ORCID: https://orcid.org/0000-0001-7053-4372)
- Yongwoo Na
- Jong-Yeon Yoo
- Se‐Bum Paik (ORCID: https://orcid.org/0000-0002-4078-305X)
- Hyunsu Do
- Jinju Han (ORCID: https://orcid.org/0000-0003-1844-2301)
- Younghee Ju
- Sarah Parylak (ORCID: https://orcid.org/0000-0003-1756-0736)
- Aidan H. McDonald
- Mingyu Ju (ORCID: https://orcid.org/0000-0002-9879-7833)
- Fred H. Gage (ORCID: https://orcid.org/0000-0002-0938-4106)
- Gregory D. Clemenson (ORCID: https://orcid.org/0000-0002-7704-8112)
- Geurim Son (ORCID: https://orcid.org/0000-0002-2470-8682)
- Dayeon Kim (ORCID: https://orcid.org/0000-0003-4873-7493)
- Jong‐Seo Kim (ORCID: https://orcid.org/0000-0002-8909-8440)
- Yong‐Mahn Han (ORCID: https://orcid.org/0000-0002-1270-0413)
- Seung‐Hee Lee
- Young‐Jin Park (ORCID: https://orcid.org/0000-0001-6684-8889)
- Joon Kim (ORCID: https://orcid.org/0000-0002-9379-3243)
- Yongsung Kim (ORCID: https://orcid.org/0000-0003-4203-9280)
- Simon T. Schafer (ORCID: https://orcid.org/0000-0002-2370-3652)
- Eunji Jung (ORCID: https://orcid.org/0000-0002-6470-6059)
- Chanhee S. Kang
- In‐Sook Ahn (ORCID: https://orcid.org/0009-0004-7923-0788)
Institutions
- Salk Institute for Biological Studies (US)
- Seoul National University (KR)
- Johns Hopkins University (US)
- Korea Advanced Institute of Science and Technology (KR)
- Johns Hopkins Medicine (US)
- Institute for Basic Science (KR)
- Institute of Cognitive and Brain Sciences (US)
- Lieber Institute for Brain Development (US)
- Hanyang University (KR)
- Orano (United States) (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1038/s42003-024-07089-2
- Citations
- 13
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- American Heart Association
- National Research Foundation
- National Research Foundation of Korea
- Institute for Basic Science
- Ministry of Science and ICT, South Korea
- National Institutes of Health
- University of California, San Diego
- National Cancer Institute