The Life History of Mitochondria in Neurons

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): 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.