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Mentor: Yuriy Usachev, PhD
Year Entered Into Program: 2006-2013
PhD Institution: University of Iowa, 2013
Mitochondria are dynamic organelles that rapidly and reversibly undergo fission and fusion (termed mitochondrial fission and fusion, or MFF). Both of these processes reflect the developmental and situational state of the cell and require a number of evolutionarily conserved proteins. Data from Stefan Strack’s lab demonstrate that reversible phosphorylation at the outer mitochondrial membrane (OMM) regulates mitochondrial shape in a bi-directional manner: phosphorylation by protein kinase A (PKA) promotes mitochondrial fusion, whereas dephosphorylation by protein phosphatase 2A (PP2A) shifts MFF equilibrium toward fission by way of the Bβ2 PP2A regulatory subunit. One proposed effect of these alterations in organelle morphology is the shaping of calcium signals. In addition to performing cellular respiration and acting as signaling platforms, mitochondria efficiently buffer and store cytosolic calcium. Accordingly, shifts in MFF equilibrium appear to be essential for controlling such Ca2+-dependent functions as synaptic plasticity and neuronal survival during/following a cytotoxic insult (stroke). My preliminary data and other data from Yuriy Usachev’s lab suggest that neuronal Ca2+ signaling is strongly affected by changes in mitochondrial architecture. The mechanisms underlying these changes, as well as pharmacological manipulation of these dynamic events are my main research interests.
Shutov LP, Kim MS, Houlihan PR, Medvedeva YV, Usachev YM.: Mitochondria and Plasma Membrane Ca2+-ATPase (PMCA) Control Presynaptic Ca2+ Clearance in Capsaicin-Sensitive Rat Sensory Neurons. J Physiol 591:2443-2462, 2013. PMCID: PMC3678036
Ulrich JD, Kim MS, Houlihan PR, Shutov LP, Mohapatra DP, Strack S, Usachev YM.: Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons. J Biol Chem 287:37594-37609, 2012. PMCID: PMC3488037
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