Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

Understanding the diverse contributions of the mitochondrial Acylglycerol Kinase (AGK) to cellular metabolism in health and disease (#531)

Thomas Jackson 1 , Daniella Hock 1 , Yilin Yang 1 , Kenji Fujihara 2 , Nicholas Clemons 2 , David Thorburn 3 , David Stroud 1 , Diana Stojanovski 1
  1. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne , Parkville, Victoria, 3010, Australia
  2. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia
  3. Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria 3052, Australia

Maintenance of correct mitochondrial metabolism requires the coordinated and regulated transport of metabolites between the cytosol and the matrix. This process is mediated by carrier proteins, which facilitate exchange of metabolites across the mitochondrial inner membrane. Biogenesis of mitochondrial carrier proteins requires an import complex known as the Translocase of the Inner Membrane 22 (TIM22 complex). Recent study of the human TIM22 complex revealed the presence of a novel subunit, acylglycerol kinase (AGK), a protein which had previously been characterised as a lipid kinase. Mutations in AGK are also known to cause Sengers syndrome, a rare and severe mitochondrial disease characterised by hypertrophic cardiomyopathy, lactic acidosis, exercise intolerance, and congenital cataracts. I have studied fibroblasts from several Sengers patients in to understand how mutations in AGK effect the function of the protein and cause disease. Proteomic analysis of these cell lines allowed us to identify a novel class of TIM22 complex substrates, called sideroflexins, and to identify characteristic programs of metabolic remodelling occurring following loss of AGK.