Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation

Mitsuhiko Katoh, Bao Wu, Huy Bang Nguyen, Truc Quynh Thai, Ryo Yamasaki, Haiyan Lu, Anna M. Rietsch, Musab M. Zorlu, Youichi Shinozaki, Yurika Saitoh, Sei Saitoh, Takashi Sakoh, Kazuhiro Ikenaka, Schuichi Koizumi, Richard M. Ransohoff, Nobuhiko Ohno

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.

Original languageEnglish
Article number4942
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

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Mitochondrial Dynamics
Microglia
Phenotype
Reactive Oxygen Species
Myelin Sheath
Mitochondria
Macrophages
Dynamins
Mitochondrial Proteins
Adenosine Monophosphate
Microtubules
Protein Kinases
Nervous System
Lipopolysaccharides
Central Nervous System
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • General

Cite this

Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation. / Katoh, Mitsuhiko; Wu, Bao; Nguyen, Huy Bang; Thai, Truc Quynh; Yamasaki, Ryo; Lu, Haiyan; Rietsch, Anna M.; Zorlu, Musab M.; Shinozaki, Youichi; Saitoh, Yurika; Saitoh, Sei; Sakoh, Takashi; Ikenaka, Kazuhiro; Koizumi, Schuichi; Ransohoff, Richard M.; Ohno, Nobuhiko.

In: Scientific reports, Vol. 7, No. 1, 4942, 01.12.2017.

Research output: Contribution to journalArticle

Katoh, M, Wu, B, Nguyen, HB, Thai, TQ, Yamasaki, R, Lu, H, Rietsch, AM, Zorlu, MM, Shinozaki, Y, Saitoh, Y, Saitoh, S, Sakoh, T, Ikenaka, K, Koizumi, S, Ransohoff, RM & Ohno, N 2017, 'Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation', Scientific reports, vol. 7, no. 1, 4942. https://doi.org/10.1038/s41598-017-05232-0
Katoh, Mitsuhiko ; Wu, Bao ; Nguyen, Huy Bang ; Thai, Truc Quynh ; Yamasaki, Ryo ; Lu, Haiyan ; Rietsch, Anna M. ; Zorlu, Musab M. ; Shinozaki, Youichi ; Saitoh, Yurika ; Saitoh, Sei ; Sakoh, Takashi ; Ikenaka, Kazuhiro ; Koizumi, Schuichi ; Ransohoff, Richard M. ; Ohno, Nobuhiko. / Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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