I research molecular mechanisms of membrane remodeling, fission and fusion in synaptic vesicle endocytosis and mitochondrial dynamics.
Research Information
Research Interests
Molecular mechanisms of membrane remodeling, fission and fusion in endocytosis and mitochondrial dynamics
Cellular membranes undergo dynamic changes in shape in remarkably striking ways during processes such as cell movement and division, and also during vesicle fission and fusion events that are integral to intracellular membrane trafficking. Large, mechanochemical GTPases of the dynamin superfamily are critically involved in many of these events including those of synaptic vesicle recycling, clathrin-mediated endocytosis, mitochondrial division and fusion, and peroxisome biogenesis. They often work in concert with membrane-sculpting BAR domain-containing proteins and various accessory molecules in effecting membrane fission and fusion. The main objective of our research is to reconstitute and elucidate the various molecular machineries and mechanisms involved in intracellular membrane remodeling, fusion and fission, specifically in synaptic vesicle endocytosis and mitochondrial dynamics, using cutting-edge state-of-the-art fluorescence spectroscopic techniques, including FRET, FCS, FLIM and related biophysical methodologies.
Publications
- Adachi Y, K Itoh, T Yamada, KL Cerveny, TL Suzuki, P Macdonald, MA Frohman, R Ramachandran, M Iijima & H Sesaki. Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division. Mol. Cell 63:1034-43, 2016.
- Osellame LD, AP Singh, DA Stroud, CS Palmer, D Stojanovski, R Ramachandran & MT Ryan. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J. Cell. Sci. 129:2170-81, 2016.
- Macdonald PJ, CA Francy, N Stepanyants, L Lehman, A Baglio, JA Mears, X Qi & R Ramachandran. Distinct Splice Variants of Dynamin-related Protein 1 Differentially Utilize Mitochondrial Fission Factor as an Effector of Cooperative GTPase Activity. J. Biol. Chem. 291:493-507, 2016.
- Stepanyants N, PJ Macdonald, CA Francy, JA Mears, X Qi & R Ramachandran. Cardiolipin's propensity for phase transition and its reorganization by dynamin-related protein 1 form a basis for mitochondrial membrane fission. Mol. Biol. Cell 26:3104-16, 2015.
- Macdonald PJ, N Stepanyants, N Mehrotra, JA Mears, X Qi, H Sesaki & R Ramachandran. A dimeric equilibrium intermediate nucleates Drp1 reassembly on mitochondrial membranes for fission. Mol. Biol. Cell 25:1905-15, 2014.
- Mehrotra N, J Nichols & R Ramachandran. Alternate pleckstrin homology domain orientations regulate dynamin-catalyzed membrane fission. Mol. Biol. Cell 25:879-90, 2014.