Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Mitochondrial Superoxide Dismutase - Signals of Distinction

Author(s): Sumitra Miriyala, Aaron K. Holley, Daret K. St Clair.

Abstract:

Mitochondrial superoxide dismutase (MnSOD) neutralizes the highly reactive superoxide radical (O2˙-), the first member in a plethora of mitochondrial reactive oxygen species (ROS). Over the past decades, research has extended the prevailing view of mitochondrion well beyond the generation of cellular energy to include its importance in cell survival and cell death. In the normal state of a cell, endogenous antioxidant enzyme systems maintain the level of reactive oxygen species generated by the mitochondrial respiratory chain. Mammalian mitochondria are important to the production of reactive oxygen species, which underlie oxidative damage in many pathological conditions and contribute to retrograde redox signaling from the organelle to the cytosol and nucleus. Mitochondria are further implicated in various metabolic and aging-related diseases that are now postulated to be caused by misregulation of physiological systems rather than pure accumulation of oxidative damage. Thus, the signaling mechanisms within mitochondria, and between the organelle and its environment, have gained interest as potential drug targets. Here, we discuss redox events in mitochondria that lead to retrograde signaling, the role of redox events in disease, and their potential to serve as therapeutic targets.

Keywords: MnSOD, Retrograde signaling, Oxidative stress, Redox signaling, Apoptotic pathways, Oxidative modification, mtDNA, TOR signaling, succinate dehydrogenase, aconitase, hypoxia, peroxynitrite, cytotoxicity, myotubes, ROS-dependent

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Article Details

VOLUME: 11
ISSUE: 2
Year: 2011
Page: [181 - 190]
Pages: 10
DOI: 10.2174/187152011795255920
Price: $58