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| Status |
Public on May 10, 2024 |
| Title |
Mdivi-1: Effective but complex mitochondrial fission inhibitor |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that p53 transcriptional network was activated while Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed, while these results were not due to mitophagy. ROS and Ca2+ levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.
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| Overall design |
RNA-seq, MC-seq was conducted in SH-SY5Y human neuroblastoma cell line and the same cell line exposed to Mdivi-1.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38581953/
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| Contributor(s) |
Ahn S, You J |
| Citation(s) |
38581953 |
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| Submission date |
Nov 02, 2023 |
| Last update date |
Aug 14, 2024 |
| Contact name |
Jueng Soo You |
| E-mail(s) |
CBnE01@gmail.com
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| Organization name |
Konkuk University
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| Street address |
120 Neungdong-ro
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| City |
seoul |
| ZIP/Postal code |
143-701 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1035077 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246902_Result_mdivil-1_vs_control.txt.gz |
62.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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