DENR

Overview

DENR (Wikidata: Q18033110), referred to in the literature as Dynamin-Related Protein 1 (DRP1) and encoded by the DNM1L gene, is a large cytosolic GTPase and master regulator of mitochondrial fission in eukaryotic cells. DRP1 belongs to the dynamin superfamily of mechanochemical enzymes and functions by oligomerizing into ring- or spiral-like structures that constrict and sever the outer mitochondrial membrane, generating smaller, discrete mitochondrial units. Under physiological conditions, DRP1 continuously cycles between the cytoplasm and the mitochondrial surface, where it is recruited to pre-existing constriction sites often marked by endoplasmic reticulum (ER) contacts and interacts with membrane-anchored receptors such as MFF, MiD49, and MiD51.

The biological importance of DRP1 extends well beyond simple organelle morphology. By governing the balance between mitochondrial fission and the opposing fusion machinery (principally Mitofusin 1 [MFN1], Mitofusin 2 [MFN2], and OPA1), DRP1 regulates mitochondrial network dynamics that are tightly coupled to cellular bioenergetics, calcium homeostasis, reactive oxygen species (ROS) production, mitophagy, and apoptosis. Post-translational modifications — including phosphorylation, SUMOylation, ubiquitination, and S-nitrosylation — fine-tune DRP1 activity and its translocation to the mitochondrial outer membrane. Dysregulation of DRP1-mediated fission has been implicated in a wide spectrum of human diseases, including neurodegenerative disorders (Alzheimer's disease, related dementia), cardiovascular disease, metabolic disease (metabolic dysfunction-associated steatohepatitis [MASH], diabetic kidney disease), polycystic ovary syndrome (PCOS), and ischemia-reperfusion injury, making it a compelling therapeutic target.

Focus of Latest Publications

Recent publications have not directly focused on DENR itself, but they do place it in the broader context of studies centered on mitochondrial dynamics, inflammatory signaling, and disease-associated stress responses. Across these reports, the main experimental emphasis was on dynamin-related protein 1 (Drp1) and related pathways in models of cerebral ischemia/reperfusion injury, metabolic dysfunction-associated steatohepatitis, polycystic ovary syndrome, Alzheimer’s disease, hepatocellular carcinoma drug resistance, inflammatory skin conditions, liver ischemia, diabetic kidney disease, and gastric cancer. In these settings, investigators used cell culture systems, rodent disease models, molecular docking, Western blotting, RT-qPCR, ELISA, microscopy, and functional assays to define how interventions altered mitochondrial morphology, oxidative stress, apoptosis, and inflammatory mediator production.

Several studies tested natural products or pharmacologic interventions that modulated Drp1-linked mitochondrial dysfunction. Fuzheng Jiedu Tongluo Granule was reported to alleviate cerebral ischemia/reperfusion injury in rats and PC12 cells by suppressing the Drp1-mediated TXNIP/NLRP3 inflammatory pathway, reducing ROS and inflammatory factors such as IL-1β and IL-18, and increasing OPA1 and TRX expression. Polygalae radix and its processed products were also associated with improved memory, reduced hippocampal damage, and enhanced antioxidant capacity in a brain aging model, with core targets including Drp1, Mfn1, Mfn2, Fis1, and BDNF. In a separate study, melatonin reversed excessive Drp1-mediated mitochondrial fission in granulosa cells from polycystic ovary syndrome models by upregulating sirtuin 1, restoring mitochondrial morphology, and lowering mitochondrial ROS.

Other publications linked Drp1-related mitochondrial remodeling to inflammatory or fibrotic disease progression and treatment resistance. In MASH, endothelial GSK3β promoted lipotoxic endotheliopathy and liver inflammation, while GSK3β deletion reduced adhesion molecules, chemokines, liver injury, inflammation, and fibrosis; mechanistically, GSK3 inhibition restored mitochondrial morphology and respiration through AMP-activated protein kinase and Drp1. In hepatocellular carcinoma, lactylation of ABHD6 promoted mitochondrial translocation of the protein, displaced DRP1 from FIS1, disrupted mitochondrial fission, and contributed to lenvatinib resistance. In gastric cancer, BATF2 overexpression restored adriamycin sensitivity by inhibiting ERK phosphorylation and downstream Drp1-dependent mitochondrial fission through a p53-linked mechanism. Additional studies reported that lemon balm-derived nanovesicles reduced cytokine production and mitochondrial fragmentation in pro-inflammatory skin fibroblasts, and that PP2A inhibition protected donor livers from prolonged cold ischemia-reperfusion injury by interfering with Drp1 translocation and ER stress.

Overall, these recent publications reinforce a recurring theme: DENR-related literature in this set is embedded in work on mitochondrial quality control, inflammatory amplification, and cell survival under stress. The studies collectively highlight Drp1 as a central node connecting mitochondrial fission to tissue injury, immune activation, and therapy resistance, with interventions ranging from herbal formulations and plant-derived nanovesicles to melatonin and pathway-specific inhibitors.

Key Publications

• May Fuzheng Jiedu Tongluo Granule Alleviates Cerebral Ischemia/reperfusion Injury-induced Inflammation By Inhibiting Drp1-mediated TXNIP/NLRP3 Pathway. (Molecular neurobiology, 2026, PMID 42113382): "Dynamin-related protein 1 (Drp1) performs an essential role in initiating and advancing CI/RI-induced inflammatory reactions."
• May Endothelial Cell Glycogen Synthase Kinase 3β Promotes Lipotoxic Endotheliopathy and Liver Inflammation in MASH. (JCI insight, 2026, PMID 42084928): "Mechanistically, GSK3 inhibition restored lipotoxicity-induced alterations in LSEC mitochondrial morphology and respiration by regulating AMP-activated protein kinase and dynamin-related protein 1."
• Jun From Chemical Discrepancy to Mechanistic Insight: UPLC-MS, Bioinformatics, and In Vivo Studies on the Anti-Brain Aging Effects of Polygalae Radix and Its Processed Products. (Biomedical chromatography : BMC, 2026, PMID 42011008): "Core targets (BDNF, Mfn1, Mfn2, Drp1, and Fis1) interacted with these components."
• May Melatonin attenuates Drp1-mediated excessive mitochondrial fission through upregulation of SIRT1 in granulosa cells in polycystic ovary syndrome. (Reproduction (Cambridge, England), 2026, PMID 41949882): "Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission is critical for maintaining intact mitochondrial function."
• May Dysregulation of Drp1 and Mfn2 is associated with reduced PSD-95, synaptophysin, and BDNF expression in a rat model of Alzheimer's disease. (International journal of biological macromolecules, 2026, PMID 41932483): "Mitochondrial dynamics, especially the balance between fusion and fission processes regulated by proteins like mitofusin 2 (Mfn2) and dynamin-related protein 1 (Drp1), play critical roles in neuronal health."
• Jun Lactylation Converts ABHD6 into a Mitochondrial Regulator That Drives Lenvatinib Resistance in Hepatocellular Carcinoma. (Cancer research, 2026, PMID 41861279): "...that competitively bound the fission regulator mitochondrial fission 1 (FIS1) and displaced dynamin-related protein 1 (DRP1)."
• Apr Lemon balm-derived nanovesicles restore mitochondrial function and reduce cytokine production in skin fibroblasts under pro-inflammatory conditions. (European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2026, PMID 41734866): "Additionally, they reduced mitochondrial fragmentation by regulating the activation of Drp1 and lowered the total p38 MAPK level."
• Apr DRP1 depletion protects NK cells from hypoxia-induced dysfunction. (Redox report : communications in free radical research, 2026, PMID 41706678): "DRP1 depletion protects NK cells from hypoxia-induced dysfunction."
• Apr PP2A inhibition alleviates DCD liver damage during prolonged cold ischemia by interfering Drp1 translocation and ER stress. (Mitochondrion, 2026, PMID 41587672): "In particular, okadaic acid (OA) inhibited the translocation of Drp1 to mitochondria and the release of Cyt c into the cytoplasm."
• Apr Suoquan Yishen formula attenuates ectopic lipid deposition in diabetic kidney disease by inhibiting UBC9-mediated SUMO1 modification of DRP1. (Journal of ethnopharmacology, 2026, PMID 41461331): "...with SUMO1-mediated modification of DRP1 functioning as a key driving mechanism."