ArticleThe Journal of biological chemistry2016
Distinct Splice Variants of Dynamin-related Protein 1 Differentially Utilize Mitochondrial Fission Factor as an Effector of Cooperative GTPase Activity.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 96 citations in OpenAlex.
- Long-read sequencing-based atlas of tissue-specific expression of DNM1L transcript variants.The FEBS journal · 2026Article
- Aberrant Splicing ofCirculation. Genomic and precision medicine · 2026Article
- Conformational Rearrangement of Fission DSPs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The Structure of the Drp1 Lattice on Membrane.Journal of molecular biology · 2025Article
- Mitochondrial fission - changing perspectives for future progress.Journal of cell science · 2025Review
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- Molecular mechanisms of mitochondrial dynamics.Nature reviews. Molecular cell biology · 2025Review
- DRP1: shedding light on the complex nexus of mitochondrial fission and breast cancer.Future oncology (London, England) · 2025Review
- Hypoxic preconditioning increases mitochondrial respiration and HFrontiers in molecular neuroscience · 2025Article
- Alternative splicing in ovarian cancer.Cell communication and signaling : CCS · 2024Review
- Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression.EMBO reports · 2024Article
- Inflammatory lung injury is associated with endothelial cell mitochondrial fission and requires the nitration of RhoA and cytoskeletal remodeling.Free radical biology & medicine · 2024Article
- Drp1: Focus on Diseases Triggered by the Mitochondrial Pathway.Cell biochemistry and biophysics · 2024Review
- Alternative splice variants of the mitochondrial fission proteinbioRxiv : the preprint server for biology · 2024Article
- Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif.Nature communications · 2024Article
- DRP1: At the Crossroads of Dysregulated Mitochondrial Dynamics and Altered Cell Signaling in Cancer Cells.ACS omega · 2023Review
- The variable domain from dynamin-related protein 1 promotes liquid-liquid phase separation that enhances its interaction with cardiolipin-containing membranes.Protein science : a publication of the Protein Society · 2023Article
- Mitochondrial Dynamics and Insulin Secretion.International journal of molecular sciences · 2023Review
- Convergent and divergent mechanisms of peroxisomal and mitochondrial division.The Journal of cell biology · 2023Article
- Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?Biochemical Society transactions · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple isoforms of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) arise from the alternative splicing of its single gene-encoded pre-mRNA transcript. Among these, the longer Drp1 isoforms, expressed selectively in neurons, bear unique polypeptide sequences within their GTPase and variable domains, known as the A-insert and the B-insert, respectively. Their functions remain unresolved. A comparison of the various biochemical and biophysical properties of the neuronally expressed isoforms with that of the ubiquitously expressed, and shortest, Drp1 isoform (Drp1-short) has revealed the effect of these inserts on Drp1 function. Utilizing various biochemical, biophysical, and cellular approaches, we find that the A- and B-inserts distinctly alter the oligomerization propensity of Drp1 in solution as well as the preferred curvature of helical Drp1 self-assembly on membranes. Consequently, these sequences also suppress Drp1 cooperative GTPase activity. Mitochondrial fission factor (Mff), a tail-anchored membrane protein of the mitochondrial outer membrane that recruits Drp1 to sites of ensuing fission, differentially stimulates the disparate Drp1 isoforms and alleviates the autoinhibitory effect imposed by these sequences on Drp1 function. Moreover, the differential stimulatory effects of Mff on Drp1 isoforms are dependent on the mitochondrial lipid, cardiolipin (CL). Although Mff stimulation of the intrinsically cooperative Drp1-short isoform is relatively modest, CL-independent, and even counter-productive at high CL concentrations, Mff stimulation of the much less cooperative longest Drp1 isoform (Drp1-long) is robust and occurs synergistically with increasing CL content. Thus, membrane-anchored Mff differentially regulates various Drp1 isoforms by functioning as an allosteric effector of cooperative GTPase activity.
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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.