miR-124 coordinates metabolic regulators acting at early stages of human neurogenesis

Autor: Geurim Son, Yongwoo Na, Yongsung Kim, Ji-Hoon Son, Gregory D. Clemenson, Simon T. Schafer, Jong-Yeon Yoo, Sarah L. Parylak, Apua Paquola, Hyunsu Do, Dayeon Kim, Insook Ahn, Mingyu Ju, Chanhee S. Kang, Younghee Ju, Eunji Jung, Aidan H. McDonald, Youngjin Park, Gilhyun Kim, Se-Bum Paik, Junho Hur, Joon Kim, Yong-Mahn Han, Seung-Hee Lee, Fred H. Gage, Jong-Seo Kim, Jinju Han
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-07089-2
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje