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Mitochondrial ROS and Apoptosis

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Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease

Abstract

Reactive oxygen species (ROS) are by-products of cellular metabolism or of xenobiotic exposure. Depending on their level, ROS can be detrimental leading to oxidative modifications in cellular lipids, proteins, or DNA or can be beneficial participating in intracellular signaling or cell regulation. Mitochondria are a quantitatively relevant intracellular source of ROS which are mainly produced as a result of monoelectron reduction of oxygen at the level of the respiratory chain complexes. Additionally, mitochondrial redox systems, such us glutathione, thioredoxin, and pyridine nucleotide redox couples, are involved in the antioxidant defense participating in modulation of mitochondrial functions including apoptotic cell death. Imbalance between ROS and the antioxidant defense leads to oxidative stress and oxidative changes to cellular biomolecules. Apoptosis or programmed cell death is initiated either at the plasma membrane (extrinsic) receptor-mediated apoptosis or at the mitochondria (intrinsic)-mediated apoptosis, respectively. High levels of mitochondrial ROS (mtROS) can initiate intrinsic apoptosis leading to the release of mitochondrial apoptogenic factors like cytochrome c, apoptosis-inducing factor, into the cytosol. Moreover, mtROS can oxidize mitochondrial glutathione (GSH) causing the loss of intramitochondrial redox homeostasis and irreversible oxidative modifications to mitochondrial macromolecules including mitochondrial DNA. In addition to glutathione, thioredoxin and thioredoxin-dependent enzymes are involved in the removal of hydrogen peroxide and in the redox regulation of mitochondrial protein functions. The reductant for these two redox systems is NADPH and mitochondrial sources, including nicotinamide nucleotide transhydrogenase, isocitrate dehydrogenase, and malic enzyme. A better understanding of the redox control of apoptosis initiation and execution could stem the development of novel therapeutic interventions for oxidative stress-associated pathologies.

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  1. Department of Medicine, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Hazem El-Osta M.D. & Magdalena L. Circu Ph.D.

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  1. Hazem El-Osta M.D.
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  1. College of Health Sciences, Midwestern University, Glendale, Arizona, USA

    Lori M. Buhlman

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El-Osta, H., Circu, M.L. (2016). Mitochondrial ROS and Apoptosis. In: Buhlman, L. (eds) Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-42139-1_1

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