Eligible Student Poster 49th Lorne Conference on Protein Structure and Function 2024

 Investigating Palmitoyl-CoA Impact on DRP1 in Mitochondrial Fission (#147)

Javaid Jabbar 1 , Christopher Langendorf 2 , John Scott 3 , Jon Oakhill 2 , Isabelle Rouiller 1 4
  1. Biochemistry and Pharmacology, The University of Melbourne, Melbourne
  2. St. Vincent's Institute of Medical Research, Melbourne
  3. Monash Institute of Pharmaceutical Sciences, Melbourne, Vic, Australia
  4. ARC Centre for Cryo-elecron Microscopy of Membrane Proteins, Melbourne

Mitochondria, also known as the powerhouses of the cell, are organelles that provide cells with chemical energy essential for anabolic biochemical processes. In response to changing energy needs of the cell, mitochondria being dynamic in nature undergo fission and fusion. It is dependent on GTPase dynamin-related protein 1 (DRP1, isoforms 1-9). DRP1 also plays a crucial role in cell differentiation, immunity, apoptosis, signalling, metabolism and aging. Crystal structure of DRP1 Isoform 2 has been solved using x-ray crystallography. However, ~100 amino acid long variable domain containing regulatory post translational modifications (PTMs) remains unresolved. Our preliminary data indicates that long chain fatty acid-CoA esters (FACE) allosterically activate DRP1 isoform 3, regulating mitochondrial fission and morphology. In this study, we will use palmitoyl-CoA to stabilize the variable domain of DRP1 and elucidate its structure using cryo-EM.