Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver
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PROVIDER: PRJNA1257844 | ENA |
REPOSITORIES: ENA
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Project description:Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are essential for lipid metabolism. In this study, liver-specific Drp1 knockout (Drp1LiKO) mice were utilized to investigate the impact of disrupted organelle interactions. Analysis revealed increased interactions between mitochondria and LDs, as well as among ER, mitochondria, and LDs in Drp1LiKO mice. As a result, impaired fatty acid metabolism was observed, leading to liver inflammation. In vitro studies using primary hepatocytes from Drp1LiKO mice further confirmed disrupted lipid metabolism and increased inflammation. These findings underscore the significance of Drp1 in maintaining organelle interactions for proper lipid metabolism and liver health. Tar-geting Drp1-mediated interactions may present a promising approach for the treatment of liver diseases associated with lipid metabolism dysregulation.
2025-05-01 | GSE296128 | GEO
Project description:Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are essential for lipid metabolism. In this study, liver-specific Drp1 knockout (Drp1LiKO) mice were utilized to investigate the impact of disrupted organelle interactions. Analysis revealed increased interactions between mitochondria and LDs, as well as among ER, mitochondria, and LDs in Drp1LiKO mice. As a result, impaired fatty acid metabolism was observed, leading to liver inflammation. In vitro studies using primary hepatocytes from Drp1LiKO mice further confirmed disrupted lipid metabolism and increased inflammation. These findings underscore the significance of Drp1 in maintaining organelle interactions for proper lipid metabolism and liver health. Targeting Drp1-mediated interactions may present a promising approach for the treatment of liver diseases associated with lipid metabolism dysregulation.
2025-05-01 | GSE296127 | GEO
Project description:Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver
| PRJNA1257843 | ENA
Project description: Not available
| S-EPMC12109831 | biostudies-literature
Project description:With the advent of exome sequencing, a growing number of children are being identified with de novo loss of function mutations in the large GTPase essential for mitochondrial fission - Dynamin Related Protein 1 (DRP1); these mutations result in severe neurodevelopmental phenotypes such as developmental delay, optic atrophy, and epileptic encephalopathies. Though it is established that mitochondrial fission is an essential precursor to the rapidly changing metabolic needs of the developing cortex, it is not understood how identified mutations in different domains of DRP1 uniquely disrupt cortical development and synaptic maturation. We leveraged the power of both high-resolution imaging and induced pluripotent stem cells (iPSCs) harboring DRP1 mutations in either the GTPase or stalk domains to model early stages of cortical development. Transcriptional profiling of mutant DRP1 cortical neurons during maturation, as well as imaging of organelle dynamics and neuronal synapses, strongly suggests that altered mitochondrial morphology of DRP1 mutant neurons affect synaptic development leading to pathogenic dysregulation of synaptic activity.
2025-06-30 | GSE296512 | GEO
Project description:Purpose:to verify Drp1-mediated biological pathways under physiological and ischemia conditions.Methods:C57BL/6 mice and Drp1 knockdown mice were used for ischemia treatment. Right femoral arteries were catheterized with polyethylene catheters for bleeding 50% of total blood volume (≈7% of weight). The ischemia time started to calculate after the model was established. A laparotomy was then carried out to obtain superior mesenteric artery tissues (SMAs) for transcriptome analysis. Series-Cluster analysis was performed to identify the global trends of mitochondrial DEGs after Drp1 knockdown. Gene ontology (GO) analysis was performed to facilitate elucidating the biological process (BP), molecular function (MF) and cellular component (CC) of unique genes in the significant or representative profiles. Results:In addition to its traditional roles in GTPase regulation and mitochondrial fission, Drp1 may also regulate actin cytoskeleton and the movement of microtubules. Besides, Drp1 may participate in the regulation of morphology and functions of other organelles, including endoplasmic reticulum, peroxisome, phagolysosome, etc. As for general organ functions, Drp1 may regulate vascular constriction and dilation. These consequences indicated the important role of Drp1 in ischemia-induced cellular regulation. Conclusions: Drp1 deficiency proves the important role of Drp1 in ischemia-induced biomedical processes through multiple potential fission-independent manners. Methods:C57BL/6 mice and Drp1 knockdown mice were used for ischemia treatment. Right femoral arteries were catheterized with polyethylene catheters for bleeding 50% of total blood volume (≈7% of weight). The ischemia time started to calculate after the model was established. A laparotomy was then carried out to obtain superior mesenteric artery tissues (SMAs) for transcriptome analysis. Series-Cluster analysis was performed to identify the global trends of mitochondrial DEGs after Drp1 knockdown. Gene ontology (GO) analysis was performed to facilitate elucidating the biological process (BP), molecular function (MF) and cellular component (CC) of unique genes in the significant or representative profiles. Results:In addition to its traditional roles in GTPase regulation and mitochondrial fission, Drp1 may also regulate actin cytoskeleton and the movement of microtubules. Besides, Drp1 may participate in the regulation of morphology and functions of other organelles, including endoplasmic reticulum, peroxisome, phagolysosome, etc. As for general organ functions, Drp1 may regulate vascular constriction and dilation. These consequences indicated the important role of Drp1 in ischemia-induced cellular regulation. Conclusions: Drp1 deficiency proves the important role of Drp1 in ischemia-induced biomedical processes through multiple potential fission-independent manners.
2020-04-29 | GSE124096 | GEO
Project description:NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.
2026-02-23 | PXD049224 | Pride
Project description:<p>Disruption of organelle interactions due to metabolic stress is a crucial factor in the pathological processes of many degenerative diseases. Current treatments usually focus on individual organelles while ignoring the role of organelle interactions in cell damage caused by cascade reactions. There is an urgent need to develop a systematic and effective method to restore homeostasis of the organelle interaction network. Compared with animal cells, the participation of chloroplasts enables plant cells to show defensive adaptation under stress. Therefore, delivering plant-derived photosynthetic systems into animal cells may help to establish a more stable organelle interaction network. In this study, plant-derived photosynthetic systems effectively restored homeostasis of the interaction network of animal organelles. Specifically, plant-derived nanothylakoid units provided energy to animal cells, regulated intracellular Ca2+ homeostasis, increased endoplasmic reticulum (ER) lipid unsaturation and global membrane fluidity, reduced abnormal contact between mitochondria and ER, and alleviated mitochondrial dysfunction. By combining implantable light-emitting diodes with wireless charging, we expanded photosynthesis therapy, enabling smarter and more effective treatments for deeper tissues. This study provides a proof-of-concept for disease treatment based on the regulation of organelle interaction networks by natural photosynthetic systems and establishes a novel therapeutic approach for treating deep tissues.</p>
2026-01-20 | MTBLS13730 | MetaboLights
Project description:Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated, when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multispectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (M-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (M-ER-P-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid synthesis. Together, we show that macrophages form functional multi-organellar units (MOUs) to support metabolic adaptation, and provide an experimental strategy to identify organelle-metabolic signaling hubs.
2024-05-03 | GSE235484 | GEO
Project description:Mitochondrial homeostasis is important for cell metabolism, growth, proliferation, and immune responses. The critical regulator for mitochondrial homeostasis, Drp1 and TFAM are frequently abnormal expression in many cancers and is closely implicated in tumorigenesis. Here, we found that Drp1 high expression or TFAM low expression is correlated with poor overall survival of ESCC patients. However, the underling mechanism by Drp1 or TFAM influence tumor progression is largely unknown, especially in esophageal squamous cell carcinoma (ESCC). To investigate the underling mechanisms of Drp1 overexpression or TFAM deficiency-mediated ESCC progression, transcriptome profiling was performed by RNA sequencing analysis in ESCC cells with Drp1 overexpression or TFAM knockdown.
2022-03-02 | GSE182710 | GEO