Mitochondria form a network that is finely tuned to the needs of the cell. Changes in mitochondrial fission and fusion are important events in cell signalling and development. However unscripted changes in the mitochondrial network can be pathological. Increased mitochondrial fission also appears to be a hallmark of disease states including Huntington's and Parkinson's and during apoptosis.
We have identified two new players of mitochondrial fission, MiD49 and MiD51, involved in recruiting the master fission mediator Dynamin related protein 1 (Drp1) to mitochondria. Using imaging, cell biology and structural biology, we are working out how the MiD proteins and other members of the morphology machinery regulate mitochondrial dynamics at the cellular and molecular level. Our findings are being used to determine how fission and fusion events may be controlled in disease states.
The discovery of Dnm2 as a mitochondrial fission protein let to a re-evaluation of the role of Drp1 in mitochondrial and peroxisomal fission. Using advanced imaging and gene-editing techniques, we are investigating the differential roles of Drp1 and Dnm2 in organelle dynamics and health.
Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission. Sukrut C. Kamerkar, Felix Kraus, Alice J. Sharpe, Thomas J. Pucadyil & Michael T. Ryan. Nature Communications Volume 9, Article number: 5239 (2018) Article Pubmed
Osellame LD, Singh AP, Stroud DA, Palmer CS, Stojanovski D, Ramachandran R, Ryan MT. Cooperative and independent roles of Drp1 adaptors Mff and MiD49/51 in mitochondrial fission. J Cell Sci. 2016 Apr 12. pii: jcs.185165. [Epub ahead of print] Pubmed
Elgass KD, Smith EA, LeGros MA, Larabell CA, Ryan MT. Analysis of ER-mitochondria contacts using correlative fluorescence microscopy and soft X-ray tomography of mammalian cells. J Cell Sci. 2015 Aug 1;128(15):2795-804. Pubmed
Richter V, Palmer CS, Osellame LD, Singh AP, Elgass K, Stroud DA, Sesaki H, Kvansakul M, Ryan MT. Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission. J Cell Biol. 2014 Feb 17;204(4):477-86. Pubmed
Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem. 2013 Sep 20;288(38):27584-93. doi: 10.1074/jbc.M113.479873. Epub 2013 Aug 6. Pubmed
Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT. MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 2011 Jun;12(6):565-73. Pubmed
Australian Research Council Discovery Grant (2016-2018)