The intermediate filament protein GFAP regulates mitochondrial fission in astrocytes
Abstract
Mitochondrial plasticity, coordinated by fission and fusion, is crucial to ensure cellular functions. Mitochondrial fission is mediated by the GTPase Drp1 at the constriction site, which is proposed to be driven by the actin–myosin contractile force. However, the mechanism that propels constriction remains unclear, and the potential involvement of additional mechanisms in this process remains an open question. Here, using structured illumination microscopy, electron microscopy, and correlative light electron microscopy (CLEM), we show that the type III intermediate filament glial fibrillary acidic protein (GFAP) participates in mitochondria constriction and fission by interacting with Drp1. Remarkably, loss of GFAP results in hyperfused mitochondria under physiological and even Ca 2+ -induced mitochondrial fission conditions. Additionally, mutations in GFAP, the cause of Alexander disease, result in more Drp1 localized to GFAP and lead to significantly increased mitochondrial fissions. Taken together, these findings propose a role of type III intermediate filaments in mitochondrial division.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Ding Xiong
Ye Sing Tan
Program in Neuroscience and Behavioural Disorders, Duke-NUS Medical School
Fang Yuan
Yinglu Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University
Kay En Low
Electron Microscopy Unit, Microscopy Cluster, Yong Loo Lin School of Medicine, National University of Singapore
Isabelle Bonne
Electron Microscopy Unit, Microscopy Cluster, Yong Loo Lin School of Medicine, National University of Singapore
Sakthikumar Mathivanan
Center for Neurologic Diseases, Sanford Burnham Prebys Medical Discovery Institute
Phil Jun Kang
Program in Neuroscience and Behavioural Disorders, Duke-NUS Medical School
Zijun Sun
Waisman Center, University of Wisconsin-Madison
Xueyan Li
Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, Beijing 100191, China
Emily Abella
Waisman Center, University of Wisconsin-Madison
Albee Messing
Waisman Center, University of Wisconsin-Madison
Linghai Kong
Waisman Center, University of Wisconsin-Madison
Su-Chun Zhang
Program in Neuroscience and Behavioural Disorders, Duke-NUS Medical School