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3 - Mitochondria, metabolic inhibitors and neurodegeneration

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
James G. Greene  and
J. Timothy Greenamyre
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
James G. Greene
Affiliation:
Center for Neurodegenerative Disease and Department of Neurology, Emory University, Atlanta, GA, USA
J. Timothy Greenamyre
Affiliation:
Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, PA, USA
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Summary

The role of the mitochondrion in neurodegeneration is a paradox. On the one hand, vital mitochondrial tasks, such as energy production and calcium buffering, provide an important foundation for all neuronal functions. Yet, on the other, mitochondrial free radical production and involvement in cell-death cascades may lead to a neuron's untimely demise.

It is now clear that mitochondria are not merely neuronal “power plants”, but are highly complex, integrated organelles whose function transcends that of simple energy production. In addition to providing the majority of neuronal energy via oxidative phosphorylation, mitochondria play a central role in intracellular ion homeostasis, free radical management, and gene and protein expression.

This chapter will focus on the biology of mitochondrial electron transport, oxidative phosphorylation and other mitochondrial functions, and will discuss the effects of mitochondrial toxins on mitochondrial function and neuronal viability. It will explore briefly one of the main consequences of oxidative metabolism, mitochondrial free radical production and how this and other mitochondrial factors potentially contribute to neuronal death.

Mitochondrial energy production and sites of action for metabolic inhibitors

Mitochondria efficiently convert the potential energy of glucose into a usable cellular energy currency, primarily ATP. Glucose is the primary basis for neuronal energy metabolism; ketone bodies can provide a limited energy source, but only in situations of chronic metabolic imbalance.

Glucose crosses the blood–brain barrier in an insulin-independent manner and is taken up by membrane transporters. It is phosphorylated almost immediately by hexokinase and enters glycolysis.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 33 - 43
Publisher: Cambridge University Press
Print publication year: 2005

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