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Volume 22
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10.3390/ijms22010410
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Article

Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome

by
Byung Geun Ha
1,†,
Jung-Yoon Heo
1,†,
Yu-Jin Jang
1,
Tae-Shin Park
1,
Ju-Yeon Choi
1,
Woo Young Jang
1,‡ and
Sung-Jin Jeong
1,2,*
1
Research Group of Developmental Disorders and Rare Diseases, Korea Brain Research Institute (KBRI), Daegu 41062, Korea
2
Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Current address: School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 41566, Korea.
Int. J. Mol. Sci. 2021, 22(1), 410; https://doi.org/10.3390/ijms22010410
Submission received: 25 November 2020 / Revised: 21 December 2020 / Accepted: 29 December 2020 / Published: 2 January 2021
(This article belongs to the Special Issue Signalling Networks Regulating Cell Survival and Dynamics in Brain Development and Disease)
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Abstract

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).
Keywords: extracellular vesicles; mitochondrial dysfunction; astrocytes; Fragile X syndrome; Fmr1 knockout mouse extracellular vesicles; mitochondrial dysfunction; astrocytes; Fragile X syndrome; Fmr1 knockout mouse

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MDPI and ACS Style

Ha, B.G.; Heo, J.-Y.; Jang, Y.-J.; Park, T.-S.; Choi, J.-Y.; Jang, W.Y.; Jeong, S.-J. Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome. Int. J. Mol. Sci. 2021, 22, 410. https://doi.org/10.3390/ijms22010410

AMA Style

Ha BG, Heo J-Y, Jang Y-J, Park T-S, Choi J-Y, Jang WY, Jeong S-J. Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome. International Journal of Molecular Sciences. 2021; 22(1):410. https://doi.org/10.3390/ijms22010410

Chicago/Turabian Style

Ha, Byung Geun, Jung-Yoon Heo, Yu-Jin Jang, Tae-Shin Park, Ju-Yeon Choi, Woo Young Jang, and Sung-Jin Jeong. 2021. "Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome" International Journal of Molecular Sciences 22, no. 1: 410. https://doi.org/10.3390/ijms22010410

APA Style

Ha, B. G., Heo, J.-Y., Jang, Y.-J., Park, T.-S., Choi, J.-Y., Jang, W. Y., & Jeong, S.-J. (2021). Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome. International Journal of Molecular Sciences, 22(1), 410. https://doi.org/10.3390/ijms22010410

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