ArticleThe Journal of biological chemistry2013
Dual function of mitochondrial Nm23-H4 protein in phosphotransfer and intermembrane lipid transfer: a cardiolipin-dependent switch.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 157 citations in OpenAlex.
- Functional Diversity and Emerging Roles of Human NME/NDPK Group II Proteins.International journal of molecular sciences · 2026Review
- Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- High tide or low tide: the transport and metabolism of mitochondrial nucleotides.The Biochemical journal · 2025Review
- What can ATP content tell us about Barth syndrome muscle phenotypes?Journal of translational genetics and genomics · 2025Article
- Dynamic death decisions: How mitochondrial dynamics shape cellular commitment to apoptosis and ferroptosis.Developmental cell · 2024Review
- Phospholipid Scramblase Activity of VDAC Dimers: New Implications for Cell Death, Autophagy and Ageing.Biomolecules · 2024Review
- Mechanistic Insights into Substrate Recognition of Human Nucleoside Diphosphate Kinase C Based on Nucleotide-Induced Structural Changes.International journal of molecular sciences · 2024Article
- Review
- Did mitophagy follow the origin of mitochondria?Autophagy · 2024Review
- NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression.EMBO reports · 2024Article
- Creation of a Curated Database of Experimentally Determined Human Protein Structures for the Identification of Its Targetome.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2024Article
- Mitochondrial GTP metabolism controls reproductive aging in C. elegans.Developmental cell · 2023Article
- Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial HPharmaceutical biology · 2023Review
- Mechanisms of action of NME metastasis suppressors - a family affair.Cancer metastasis reviews · 2023Review
- A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated With DCM.JACC. Asia · 2023Review
- LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs.Autophagy · 2022Article
- Mitochondria and their potential role in acute lung injury (Review).Experimental and therapeutic medicine · 2022Review
- The Complex Functions of the NME Family-A Matter of Location and Molecular Activity.International journal of molecular sciences · 2021Article
- NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix.Cell & bioscience · 2021Article
- The mitochondrially-localized nucleoside diphosphate kinase D (NME4) is a novel metastasis suppressor.BMC biology · 2021Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
The nucleoside diphosphate kinase Nm23-H4/NDPK-D forms symmetrical hexameric complexes in the mitochondrial intermembrane space with phosphotransfer activity using mitochondrial ATP to regenerate nucleoside triphosphates. We demonstrate the complex formation between Nm23-H4 and mitochondrial GTPase OPA1 in rat liver, suggesting its involvement in local and direct GTP delivery. Similar to OPA1, Nm23-H4 is further known to strongly bind in vitro to anionic phospholipids, mainly cardiolipin, and in vivo to the inner mitochondrial membrane. We show here that such protein-lipid complexes inhibit nucleoside diphosphate kinase activity but are necessary for another function of Nm23-H4, selective intermembrane lipid transfer. Mitochondrial lipid distribution was analyzed by liquid chromatography-mass spectrometry using HeLa cells expressing either wild-type Nm23-H4 or a membrane binding-deficient mutant at a site predicted based on molecular modeling to be crucial for cardiolipin binding and transfer mechanism. We found that wild type, but not the mutant enzyme, selectively increased the content of cardiolipin in the outer mitochondrial membrane, but the distribution of other more abundant phospholipids (e.g. phosphatidylcholine) remained unchanged. HeLa cells expressing the wild-type enzyme showed increased accumulation of Bax in mitochondria and were sensitized to rotenone-induced apoptosis as revealed by stimulated release of cytochrome c into the cytosol, elevated caspase 3/7 activity, and increased annexin V binding. Based on these data and molecular modeling, we propose that Nm23-H4 acts as a lipid-dependent mitochondrial switch with dual function in phosphotransfer serving local GTP supply and cardiolipin transfer for apoptotic signaling and putative other functions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.