Reconstituting the pathway to mitochondrial division

Abstract

Mitochondria are double membrane organelles in eukaryotes whose primaryfunction is energy production through oxidative phosphorylation Mitochondria havea diverse morphology which is maintained by the cycles of division and fusion Asmitochondria cannot be synthesized de novo they rely on fission for successfulorganelle inheritance Moreover mitochondrial division is also essential for themaintenance of the cellular homeostasis during cell death and is used as a tool tosegregate damaged mitochondria Dynamin related protein 1 Drp1 a member of thedynamin superfamily of proteins is a crucial player involved in the mitochondrialdivision process In the absence of Drp1 mitochondria show an elongated phenotype which is reminiscent of a defective division process Apart from its role in themitochondrial division Drp1 is also shown to be involved in the division ofperoxisomes The domain architecture of Drp1 is similar to that of classical dynamins which consists of a GTPase domain at the N terminus bundle signaling element andthe stalk domain However instead of the lipid binding pleckstrin homology domainfound in classical dynamins Drp1 has a variable unstructured 100 amino acid loopcalled the B insert which is involved in binding to the mitochondrial lipid cardiolipin Drp1 self assembles into helical scaffolds and utilizes energy derived form GTPhydrolysisto remodel GUVs and liposomes to tubular intermediates Currentliterature indicates that Drp1 is involved in membrane remodeling to facilitate fissionbut its direct involvement in the fission process remains debated Drp1 is predominantly cytosolic and relies on mitochondrial adaptor proteins Mff MiD49 and MiD51 for its recruitment to the mitochondria Studiesdemonstrate that these adaptor proteins can act independently to recruit Drp1 However their contribution beyond recruiting Drp1 to mitochondrial and to th newline newline