Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

47-POS Board 16 STRUCTURE INSIGHT OF DRP1 DECORATED MEMBRANE TUBULES

Ruizhi Peng 1 ; Kristy Rochon 2 ; Scott M Stagg 1 ; Jason A Mears 2 ; 1 Florida State University, Institute of Molecular Biophysics, Tallahassee, FL, USA 2 Case Western Reserve University, Department of Pharmacology, Cleveland, OH, USA

Drp1, a large, cytosolic GTPase, plays a key role in mitochondrial fission, a process crucial for apoptosis, damage isolation, and the preservation of mitochondrial health. The dysregulation of mitochondrial dynamics, particularly involving Drp1, has been linked to a variety of diseases. Previous studies showed that Drp1 assembles into polymers on mitochondria outer membrane and constrict upon GTP hydrolysis. However, the precise molecular mechanism by which Drp1 remodels membranes remains a subject of ongoing research. Previous structural studies on Drp1 decoreated membranes have been hindered by heterogeneity. In this study, we utilized our uniquely developed image processing method, RASTR, to achieve sub-nanometer resolution of Drp1-decorated tubules. Our findings indicate that Drp1 forms oligomers with a geometry similar to dynamin helices on lipid templates. We discovered that Drp1 displays local order on membrane tubules, but varying spacing between stalk rungs is observed in three distinct classes of Drp1 structure. These structures provide valuable insights into the arrangement of Drp1 domains and suggest potential conformational change of GTPase domains in accordance with curvature. Together, our findings provide a better understanding of the molecular mechanism of Drp1-mediated mitochondria fission. The observed conformational changes highlight rearrangements in Drp1 domains that promote mechanochemical constriction.

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