Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

Back

Melatonin, Mitochondrial Homeostasis and Mitochondrial-Related Diseases

Author(s): Dario Acuna Castroviejo, Germaine Escames, Angel Carazo, Josefa Leon, Huda Khaldy, Russel J. Reiter.

Abstract:

The recently described ‘hydrogen hypothesis’ invokes metabolic symbiosis as the driving force for a symbiotic association between an anaerobic, strictly hydrogen-dependent organism (the host) and an eubacterium (the symbiont) that is able to respire, but which generates molecular hydrogen as an end product of anaerobic metabolism. The resulting proto-eukaryotic cell would have acquired the essentials of eukaryotic energy metabolism, evolving not only aerobic respiration, but also the cost of oxygen consumption, i.e., generation of reactive oxygen species (ROS) and oxidative damage. Mitochondria contain their own genome with a modified genetic code that is highly conserved among mammals. Control of gene expression suggests that transcription of certain mitochondrial genes may be regulated in response to the redox potential of the mitochondrial membrane. Mitochondria are involved in energy production and conservation, and they have an uncoupling mechanism to produce heat instead of ATP. Al so, mitochondria are involved in programmed cell death. Increasing evidence suggests the participation of mitochondria in neurodegenerative and neuromuscular diseases involving alterations in both nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is now known as a powerful antioxidant and increasing experimental evidence shows its beneficial effects against oxidative stress-induced macromolecular damage and diseases, including those in which mitochondrial function is affected. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies.

Keywords: Mitochondrial Homeostasis, hydrogen-dependent organism, macromolecular damage, 8-Hydroxydeoxyguanosine, Calcium-camodulin complex, Ubiquinone, Cytochrome, Superoxide anion, Peroxynitrite, Glutathione peroxidase, Dopamine

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 2
ISSUE: 2
Year: 2002
Page: [133 - 151]
Pages: 19
DOI: 10.2174/1568026023394344
Price: $58