title: Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders.
abstract: 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.
authors: Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; Research Ring on Oxidative Stress in the Nervous System, Universidad de Chile, Santiago, Chile.
authors: Natalia P
authors: NP
authors: Mena
authors: Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; Research Ring on Oxidative Stress in the Nervous System, Universidad de Chile, Santiago, Chile.
authors: Pamela J
authors: PJ
authors: Urrutia
authors: Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; Research Ring on Oxidative Stress in the Nervous System, Universidad de Chile, Santiago, Chile.
authors: Fernanda
authors: F
authors: Lourido
authors: Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; Research Ring on Oxidative Stress in the Nervous System, Universidad de Chile, Santiago, Chile.
authors: Carlos M
authors: CM
authors: Carrasco
authors: Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; Research Ring on Oxidative Stress in the Nervous System, Universidad de Chile, Santiago, Chile. Electronic address: mnunez@uchile.cl.
authors: Marco T
authors: MT
authors: Núñez
mesh_terms: D000818:Animals; D016923:Cell Death; D006418:Heme / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity
chemical_list: D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species; D006418:Heme; D007501:Iron
keywords: Heme; Iron–sulfur cluster; Mitochondrial iron homeostasis; Neurodegenerative disease; Reactive oxygen species