A Novel Interaction between MFN2/Marf and MARK4/PAR-1 Is Implicated in Synaptic Defects and Mitochondrial Dysfunction
DC Field | Value | Language |
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dc.contributor.author | Cheon, Yeongmi | - |
dc.contributor.author | Yoon, Sunggyu | - |
dc.contributor.author | Lee, Jae-Hyuk | - |
dc.contributor.author | Kim, Kiyoung | - |
dc.contributor.author | Kim, Hyung-Jun | - |
dc.contributor.author | Hong, Sung Wook | - |
dc.contributor.author | Yun, Ye -Rang | - |
dc.contributor.author | Shim, Jiwon | - |
dc.contributor.author | Kim, Sung-Hak | - |
dc.contributor.author | Lu, Bingwei | - |
dc.contributor.author | Lee, Mihye | - |
dc.contributor.author | Lee, Seongsoo | - |
dc.date.accessioned | 2023-12-14T06:31:15Z | - |
dc.date.available | 2023-12-14T06:31:15Z | - |
dc.date.issued | 2023-08 | - |
dc.identifier.issn | 2373-2822 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/25478 | - |
dc.description.abstract | (Marf), plays a role in mitochondrial fusion, mutations of which are implicated in age-related human diseases, including several neurodegenerative disorders. However, the regulation of MFN2/Marf-mediated mitochondrial fusion, as well as the pathologic mechanism of neurodegeneration, is not clearly understood. Here, we identi-fied a novel interaction between MFN2/Marf and microtubule affinity-regulating kinase 4 (MARK4)/PAR-1. In the Drosophila larval neuromuscular junction, muscle-specific overexpression of MFN2/Marf decreased the number of synaptic boutons, and the loss of MARK4/PAR-1 alleviated the synaptic defects of MFN2/Marf overexpression. Downregulation of MARK4/PAR-1 rescued the mitochondrial hyperfusion phenotype caused by MFN2/Marf overexpression in the Drosophila muscles as well as in the cultured cells. In addition, knock-down of MARK4/PAR-1 rescued the respiratory dysfunction of mitochondria induced by MFN2/Marf overex-pression in mammalian cells. Together, our results indicate that the interaction between MFN2/Marf and MARK4/PAR-1 is fine-tuned to maintain synaptic integrity and mitochondrial homeostasis, and its dysregula-tion may be implicated in neurologic pathogenesis.Significance StatementWe identified a novel interaction between MFN2/Marf and kinase MARK4/PAR-1 in Drosophila and mamma-lian cells. The MFN2/Marf and MARK4/PAR-1 interaction was critical for maintaining the synaptic structure of neuromuscular junctions in Drosophila. In addition, we found that concomitant knockdown of MARK4/ PAR-1 could rescue the mitochondrial hyperfusion and aberrant respiratory function caused by MFN2/Marf overexpression. Our study provides new insights into the link between mitochondrial defects and neurode-generation, which makes a significant contribution to the understanding of neurologic pathogenesis and therapeutic development. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | SOC NEUROSCIENCE | - |
dc.title | A Novel Interaction between MFN2/Marf and MARK4/PAR-1 Is Implicated in Synaptic Defects and Mitochondrial Dysfunction | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1523/ENEURO.0409-22.2023 | - |
dc.identifier.scopusid | 2-s2.0-85168315825 | - |
dc.identifier.wosid | 001053216000002 | - |
dc.identifier.bibliographicCitation | ENEURO, v.10, no.8 | - |
dc.citation.title | ENEURO | - |
dc.citation.volume | 10 | - |
dc.citation.number | 8 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.subject.keywordPlus | AFFINITY-REGULATING KINASE | - |
dc.subject.keywordPlus | TAU | - |
dc.subject.keywordPlus | DYNAMICS | - |
dc.subject.keywordPlus | TISSUES | - |
dc.subject.keywordPlus | FUSION | - |
dc.subject.keywordPlus | MARK4 | - |
dc.subject.keywordAuthor | Drosophila melanogaster | - |
dc.subject.keywordAuthor | MARK4/PAR-1 | - |
dc.subject.keywordAuthor | MFN2/Marf | - |
dc.subject.keywordAuthor | mitochondrial dynamics | - |
dc.subject.keywordAuthor | neurodegenerative disease | - |
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