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Vol. 54, Issue 1, 101-128, March 2002
Laboratory of Intracellular Ion Channels (A.S.) and Laboratory of
Bioenergetics, Biomembranes and Metabolic Regulations (L.W.),
Department of Cellular Biochemistry, Nencki Institute of Experimental
Biology, Polish Academy of Sciences, Warsaw, Poland
I. Introduction
II. Mitochondria and the Cell
III. Mitochondria in Chemotherapy-Induced Apoptosis
A. The Mitochondrial Pathway of Apoptosis
B. Mitochondria as Targets in the Control of Apoptosis
C. Antitumor Drugs as Apoptosis Promoters
IV. Mitochondria and Oxidative Stress, Aging, and Degenerative
Diseases
V. Interaction of Potassium Channel Openers with Mitochondria
A. Potassium Channel Openers and Mitochondrial K+
Channels
B. Mitochondrial ATP-Regulated Potassium Channel: A Novel Effector
of Cardioprotection
VI. Sulfonylureas and Mitochondria
A. Functional Effects of Antidiabetic Sulfonylureas on Mitochondria
B. Effect of Antitumor Sulfonylureas on Mitochondria
VII. The Mitochondrial Benzodiazepine Receptor
VIII. Immunosuppressant Drugs and Mitochondria
IX. Disruption of Mitochondrial Functions by Antiviral Drugs
X. Nonsteroidal Anti-Inflammatory Drugs and Mitochondria
XI. Local Anesthetics and Mitochondrial Energy Metabolism
XII. Mitochondria as a Pharmacological Target of Lipid Metabolism
A. Inhibition of the Transfer of "Activated" Fatty Acids into
Mitochondria and of Their 
-Oxidation
B. L-Carnitine Supplementation
C. Nonesterified Fatty Acids as "Natural" Uncouplers: Role in
Thermogenesis and Obesity Control
D. N-Acylethanolamines
XIII. Final Remarks
Acknowledgments
References
Mitochondria play a central role in energy metabolism within the cell. Mitochondrial dysfunctions lead to various neurodegenerative disorders and to the so-called "mitochondrial diseases". A vast amount of evidence points to the implication of mitochondria in such complex processes as apoptosis and cardioprotection. The purpose of this review is to present a recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria. These include antitumor, immunosuppressant, and antiviral drugs, potassium channel openers, sulfonylureas, and anesthetics. Some of these substances are specifically designed to affect mitochondrial functions. In other cases, drugs with primary targets in other cellular locations may modify mitochondrial functions as side effects. In any case, identification of mitochondria as primary or secondary targets of a drug may help us to better understand the drug's mechanism of action and open new perspectives for its application. As far as possible, the molecular mechanisms of the interference of particular drugs in the mitochondrial metabolism will be described. In some cases, metabolic routes in which the drugs interfere will also be briefly outlined.
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