ArticleCirculation2018
Epigenetic Dysregulation of the Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension: Mechanistic and Therapeutic Implications.
Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 157 citations in OpenAlex.
- IL-10-STAT3 axis preserves epithelial mitochondrial homeostasis during bacterial challenge.Gut microbes · 2026Article
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- Dynamin 2 Regulates Mitochondrial Mitotic Fission in Pulmonary Hypertension.Circulation research · 2026Article
- PAK5 drives vascular remodeling in hypoxic pulmonary hypertension via Drp1-dependent mitochondrial midzone division.Scientific reports · 2026Article
- Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
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- Mitochondrial dysfunction in aortic aneurysm and dissection: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Hypoxic microenvironment and pulmonary hypertension.Respiratory research · 2025Review
- Narrative review of mitochondrial dysfunction in aging-related salt-sensitive hypertension: outcomes, mechanisms, and therapeutic implications.Aging advances · 2025Article
- Protein kinase ROCK1 activates mitochondrial fission linking to oxidative stress and muscle atrophy.Kidney international · 2025Article
- Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2025Review
- Critical role of mitochondrial dynamics in chronic respiratory diseases and new therapeutic directions.Chinese medical journal · 2025Review
- miR‑34a induces apoptosis and pyroptosis in D‑Galactose‑induced aging cochlear hair cells via inhibiting TFAM and promoting mitochondrial dysfunctionInternational journal of molecular medicine · 2025Article
- Tet Methylcytosine Dioxygenase 2 (TET2) Mutation Drives a Global Hypermethylation Signature in Patients With Pulmonary Arterial Hypertension (PAH): Correlation With Altered Gene Expression Relevant to a Common T Cell Phenotype.Comprehensive Physiology · 2025Article
- Emerging insights into pulmonary hypertension: the potential role of mitochondrial dysfunction and redox homeostasis.Molecular and cellular biochemistry · 2025Review
- Exploring the interplay between mitochondria and endoplasmic reticulum in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Review
- Emodin Alleviates Monocrotaline-Induced Pulmonary Arterial Hypertension by Directly Targeting TAK1.Drug design, development and therapy · 2025Article
- Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces.Nature cell biology · 2024Article
- Nr1d1 inhibition mitigates intermittent hypoxia-induced pulmonary hypertension via Dusp1-mediated Erk1/2 deactivation and mitochondrial fission attenuation.Cell death discovery · 2024Article
- Novel Drp1 GTPase Inhibitor, Drpitor1a: Efficacy in Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitotic fission is increased in pulmonary arterial hypertension (PAH), a hyperproliferative, apoptosis-resistant disease. The fission mediator dynamin-related protein 1 (Drp1) must complex with adaptor proteins to cause fission. Drp1-induced fission has been therapeutically targeted in experimental PAH. Here, we examine the role of 2 recently discovered, poorly understood Drp1 adapter proteins, mitochondrial dynamics protein of 49 and 51 kDa (MiD49 and MiD51), in normal vascular cells and explore their dysregulation in PAH.
methodsImmunoblots of pulmonary artery smooth muscle cells (control, n=6; PAH, n=8) and immunohistochemistry of lung sections (control, n=6; PAH, n=6) were used to assess the expression of MiD49 and MiD51. The effects of manipulating MiDs on cell proliferation, cell cycle, and apoptosis were assessed in human and rodent PAH pulmonary artery smooth muscle cells with flow cytometry. Mitochondrial fission was studied by confocal imaging. A microRNA (miR) involved in the regulation of MiD expression was identified using microarray techniques and in silico analyses. The expression of circulatory miR was assessed with quantitative reverse transcription-polymerase chain reaction in healthy volunteers (HVs) versus patients with PAH from Sheffield, UK (plasma: HV, n=29, PAH, n=27; whole blood: HV, n=11, PAH, n=14) and then confirmed in a cohort from Beijing, China (plasma: HV, n=19, PAH, n=36; whole blood: HV, n=20, PAH, n=39). This work was replicated in monocrotaline and Sugen 5416-hypoxia, preclinical PAH models. Small interfering RNAs targeting MiDs or an miR mimic were nebulized to rats with monocrotaline-induced PAH (n=4-10).
resultsMiD expression is increased in PAH pulmonary artery smooth muscle cells, which accelerates Drp1-mediated mitotic fission, increases cell proliferation, and decreases apoptosis. Silencing MiDs (but not other Drp1 binding partners, fission 1 or mitochondrial fission factor) promotes mitochondrial fusion and causes G1-phase cell cycle arrest through extracellular signal-regulated kinases 1/2- and cyclin-dependent kinase 4-dependent mechanisms. Augmenting MiDs in normal cells causes fission and recapitulates the PAH phenotype. MiD upregulation results from decreased miR-34a-3p expression. Circulatory miR-34a-3p expression is decreased in both patients with PAH and preclinical models of PAH. Silencing MiDs or augmenting miR-34a-3p regresses experimental PAH.
conclusionsIn health, MiDs regulate Drp1-mediated fission, whereas in disease, epigenetic upregulation of MiDs increases mitotic fission, which drives pathological proliferation and apoptosis resistance. The miR-34a-3p-MiD pathway offers new therapeutic targets for PAH.
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