Dr. Diana STOJANOVSKI, PhD
School of Biomedical Sciences, The University of Melbourne
Molecular mechanisms underscoring SLC25A13 biogenesis.
Citrin deficiency is caused by mutation of the mitochondrial carrier protein SLC25A13. Although SLC25A13 shares characteristics of other mitochondrial carriers, it exposes a large calcium-binding domain into the mitochondrial intermembrane space. Little is known about the biogenesis of SLC25A13, that is the mechanisms of proteins transport and integration into the mitochondrial inner membrane. The impact of SLC25A13 mutation on the protein’s biogenesis pathway remain unclear.
This project will provide insight into the mechanisms overseeing the biogenesis of wild-type and mutant versions of SLC25A13, from the synthesis in the cytosol to the targeting and translocation across the mitochondrial outer membrane, followed by insertion into the mitochondrial inner membrane. Our labs expertise in the TIM22 complex and general mitochondrial import mechanisms puts us in a strong position to elucidate these mechanisms that are of direct relevance to find strategies to treat citrin deficiency. As part of this research program we will also investigate the use of a mRNA-based therapy approach for citrin deficiency.
This work has a broad impact including: (i) knowledge expansion in the biology of SLC25A13 and Citrin Deficiency; (ii) creation of cell models of disease to uncover pathomechanisms underscoring Citrin Deficiency; (iii) expanding research efforts of the Citrin Foundation through our lab’s contribute to the Foundation’s mission.
(Updated June 2022)
Dr Diana Stojanovski is a mitochondrial biologist located in the Department of Biochemistry and Pharmacology at the University of Melbourne and the Bio21 Institute. Dr Stojanovski obtained her PhD from La Trobe University in 2006 where she worked with Prof. Mike Ryan on the emerging topic of mitochondrial dynamics. In 2006, she moved to the University of Freiburg as an Alexander von Humboldt research fellow working with Prof. Nikolaus Pfanner on protein translocation systems in yeast mitochondria. Diana returned to La Trobe University in 2009 as an Australian post-doctoral fellow and in 2013 she was recruited to the University of Melbourne to start her independent research group.