Mitochondria are semi-autonomous organelles essential for the function of all mammalian tissues. In order to support cell function, mitochondria have to be delivered to the site of energy demand, and are presumably retrieved when they reach the end of their effective life. The architecture of neurons is such that the effective delivery and retrieval of mitochondria from the distal parts of projection neurons represents a significant challenge and a remarkable accomplishment. However, the mechanisms by which this challenge is met, together with the most basic information of the birth, life and death of mitochondria, is poorly understood in the context of central neurons. The central theses of this project are (a) that the normal generation, delivery, retrieval and degradation of mitochondria (collectively termed """"""""mitochondrial homeostasis"""""""") are essential for the maintenance of neuronal function, (b) that these processes are regulated to support changes in neuronal function, and (c) that neurotoxins may injure neurons in part by interfering with one or more of these processes. We will start to address these concepts in the following experimental questions: 1) What are the basic properties of mitochondrial delivery and retrieval in healthy neurons? 2) Do neurotoxins alter mitochondrial movement?, 3) Is mitochondrial biogenesis restricted to neuronal cell bodies, and is biogenesis altered by injury? and 4) Where are mitochondria degraded? Addressing these questions will provide an unprecedented insight into the life history of mitochondria in central neurons, and will highlight an important new parameter for consideration in the mechanism underlying neurodegenerative disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS049560-02
Application #
6942931
Study Section
Special Emphasis Panel (ZRG1-MDCN-A (09))
Program Officer
Refolo, Lorenzo
Project Start
2004-09-01
Project End
2008-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$342,020
Indirect Cost
Name
University of Pittsburgh
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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