ArticleCell death & disease2021
Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Microplastic-Induced DRP1-BAX Interaction Contributes to Mitochondrial Apoptosis in Lung Epithelial Cells.Environment & health (Washington, D.C.) · 2026Article
- Mitochondrial protein COXFA4L3 (C15ORF48) confers resistance to DNA-damaging anticancer agents by repressing mitochondrial DNA damage responses.Scientific reports · 2026Article
- Mitochondrial flagella-like extensions (MitoFLARE) dysfunction triggers STING-mediated immune dysregulation in sepsis.Nature communications · 2026Article
- ROS-responsive hydrogel microspheres deliver shTMEM2-loaded liposomes to suppress pyroptosis and ameliorate intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Microvesicle release drives cycles of mitophagy flux disruption and inflammatory amplification in sepsis-induced myocardial dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Renal-targeted tFNA-TPP nanoagonist treats acute kidney injury by amplifying mitophagy.Materials today. Bio · 2026Article
- From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases.Cell communication and signaling : CCS · 2026Review
- Targeted knockdown of Piezo1 in synovial macrophages attenuates osteoarthritis development.Journal of orthopaedic translation · 2026Article
- Reductive stress in cancer immunology and targeted therapy.Acta biochimica et biophysica Sinica · 2026Review
- Mitochondria: the central hub linking exercise to enhanced cardiac function.Frontiers in physiology · 2026Review
- Synaptotagmin-7 drives stress-induced cardiomyocyte necroptosis via the p53-Bak-mPTP axis.Theranostics · 2026Article
- 4-phenylbutyric acid alleviated sepsis-induced myocardial dysfunction by inhibition of MAM formation to improve mitochondrial dynamic balance in myocardial cells.Burns & trauma · 2026Article
- Article
- Oxytocin Regulated Neuroinflammation through OTR/Mitochondria Mediated Pathway to Improve Hypoxia-Induced Brain Injury.Molecular neurobiology · 2025Article
- FL3 mitigates cardiac ischemia-reperfusion injury by promoting mitochondrial fusion to restore calcium homeostasis.Cell death discovery · 2025Article
- Arginase 1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction.Signal transduction and targeted therapy · 2025Article
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- Metabolic Adaptations and Therapies in Cardiac Hypoxia: Mechanisms and Clinical Implications/ Potential Strategies.JACC. Basic to translational science · 2025Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial mass imbalance is one of the key causes of cardiovascular dysfunction after hypoxia. The activation of dynamin-related protein 1 (Drp1), as well as its mitochondrial translocation, play important roles in the changes of both mitochondrial morphology and mitochondrial functions after hypoxia. However, in addition to mediating mitochondrial fission, whether Drp1 has other regulatory roles in mitochondrial homeostasis after mitochondrial translocation is unknown. In this study, we performed a series of interaction and colocalization assays and found that, after mitochondrial translocation, Drp1 may promote the excessive opening of the mitochondrial permeability transition pore (mPTP) after hypoxia. Firstly, mitochondrial Drp1 maximumly recognizes mPTP channels by binding Bcl-2-associated X protein (BAX) and a phosphate carrier protein (PiC) in the mPTP. Then, leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) is recruited, whose kinase activity is inhibited by direct binding with mitochondrial Drp1 after hypoxia. Subsequently, the mPTP-related protein hexokinase 2 (HK2) is inactivated at Thr-473 and dissociates from the mitochondrial membrane, ultimately causing structural disruption and overopening of mPTP, which aggravates mitochondrial and cellular dysfunction after hypoxia. Thus, our study interprets the dual direct regulation of mitochondrial Drp1 on mitochondrial morphology and functions after hypoxia and proposes a new mitochondrial fission-independent mechanism for the role of Drp1 after its translocation in hypoxic injury.
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