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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/29535

Title: Elevated Intracellular Ca2+ Alters Mitochondrial Protein Import and the Accumulation of Intramitochondrial Proteins in Neurons
Authors: Nahirny, Adrian
Advisor: Mills, Linda
Department: Physiology
Keywords: mitochondria
calcium
neuron
calcium
ionophore
calcium
A23187
degradation
Issue Date: 23-Aug-2011
Abstract: Most (99%) mitochondrial proteins are nuclear-encoded and must be imported into mitochondria. Deficits in mitochondrial protein import (MPI) affect mitochondrial function and can cause neurodegenerative diseases. I hypothesized that MPI was regulated by iCa2+. In differentiated PC12 cells, treatment with the Ca2+ ionophore (A23187; 24h, 0.15uM) increased iCa2+, ROS generation and promoted neurite outgrowth. Western blot and flow cytometry in live cells showed that A23187 increased levels of mitochondrial proteins; mtHSP70 and mtGFP in mitochondria and autoradiography confirmed that A23187 increased the import of mtGFP. A23187 also slowed intramitochondrial mtGFP degradation. Increased MPI was not associated with mitochondrial biogenesis, but appeared partially dependent on cAMP. In rat cortical neurons, mtHSP70 also increased after A23187 treatment. These results show that, in neurons, increased iCa2+ can regulate MPI. Further, increased iCa2+ can slow intramitochondrial protein degradation. These results indicate that MPI is labile and may be altered in response to neuronal activity.
URI: http://hdl.handle.net/1807/29535
Appears in Collections:Master

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