ArticleProceedings of the National Academy of Sciences of the United States of America2021
NMR identification of a conserved Drp1 cardiolipin-binding motif essential for stress-induced mitochondrial fission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 75 citations in OpenAlex.
- Article
- A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.Aging cell · 2026Article
- PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.Autophagy · 2026Article
- Recombinant protein platform for high-throughput investigation of peptide-liposome interactions via fluorescence anisotropy depolarization.Communications chemistry · 2026Article
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- A membrane insertion code for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial fission during mitophagy requires both inner and outer mitofissins.EMBO reports · 2026Article
- Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions.Biomolecules · 2026Review
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- Cardiolipin and mitochondrial membrane integrity in neurodegeneration: insights from α-synuclein-driven Parkinson's disease.Acta neuropathologica communications · 2025Review
- Review
- Dynamin-like Proteins Combine Mechano-constriction and Membrane Remodeling to Enable Two-Step Mitochondrial Fission via a "Snap-through" Instability.Journal of the American Chemical Society · 2025Article
- The role of cardiolipin in mitochondrial dynamics and quality control in neuronal ischemia/reperfusion injury.Cell death & disease · 2025Review
- The Structure of the Drp1 Lattice on Membrane.Journal of molecular biology · 2025Article
- ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deciphering the language of mingling lipids and proteins.Current opinion in structural biology · 2025Review
- Membrane Association of Intrinsically Disordered Proteins.Annual review of biophysics · 2025Review
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- Acute diacylglycerol production activates critical membrane-shaping proteins leading to mitochondrial tubulation and fission.Nature communications · 2025Article
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14 authors at 4 institutions in 3 countries.
Funding
Abstract
Mitochondria form tubular networks that undergo coordinated cycles of fission and fusion. Emerging evidence suggests that a direct yet unresolved interaction of the mechanoenzymatic GTPase dynamin-related protein 1 (Drp1) with mitochondrial outer membrane-localized cardiolipin (CL), externalized under stress conditions including mitophagy, catalyzes essential mitochondrial hyperfragmentation. Here, using a comprehensive set of structural, biophysical, and cell biological tools, we have uncovered a CL-binding motif (CBM) conserved between the Drp1 variable domain (VD) and the unrelated ADP/ATP carrier (AAC/ANT) that intercalates into the membrane core to effect specific CL interactions. CBM mutations that weaken VD-CL interactions manifestly impair Drp1-dependent fission under stress conditions and induce "donut" mitochondria formation. Importantly, VD membrane insertion and GTP-dependent conformational rearrangements mediate only transient CL nonbilayer topological forays and high local membrane constriction, indicating that Drp1-CL interactions alone are insufficient for fission. Our studies establish the structural and mechanistic bases of Drp1-CL interactions in stress-induced mitochondrial fission.
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