Journal
MITOCHONDRION
Volume 21, Issue -, Pages 92-105Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2015.02.001
Keywords
Mitochondrial iron homeostasis; Iron-sulfur cluster; Heme; Reactive oxygen species; Neurodegenerative disease
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Funding
- National Council for Scientific and Technological Research of Chile: FONDECYT [1130068]
- Program of Associative Research [ACT1114]
- CONICYT [3654593]
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Synthesis of the iron-containing prosthetic groups heme and iron-sulfur clusters occurs in mitochondria. The mitochondrion is also an important producer of reactive oxygen species (ROS), which are derived from electrons leaking from the electron transport chain. The coexistence of both ROS and iron in the secluded space of the mitochondrion makes this organelle particularly prone to oxidative damage. Here, we review the elements that configure mitochondrial iron homeostasis and discuss the principles of iron-mediated ROS generation in mitochondria. We also review the evidence for mitochondrial dysfunction and iron accumulation in Alzheimer's disease, Huntington Disease, Friedreich's ataxia, and in particular Parkinson's disease. We postulate that a positive feedback loop of mitochondrial dysfunction, iron accumulation, and ROS production accounts for the process of cell death in various neurodegenerative diseases in which these features are present. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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