caa a22 4500 445376716 CHVBK 20180317143005.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00702-010-0503-7 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0503-7 Iron-dependent functions of mitochondria—relation to neurodegeneration [Elektronische Daten] [Gabriele Gille, Heinz Reichmann] A number of neurodegenerative diseases are associated with iron dyshomeostasis and mitochondrial dysfunction. However, the pathomechanistic interplay between iron and mitochondria varies. This review summarises the physiological role of iron in mitochondria and subsequently exemplifies two neurodegenerative diseases with disturbed iron function in mitochondria: inherited Friedreich ataxia (FRDA) and idiopathic Parkinson disease (PD). In eukaryotes, mitochondria are main consumers of iron. The respiratory chain relies on iron-containing redox systems in the form of complexes I-III with iron-sulphur clusters and cytochromes with haem as prosthetic groups. The bifunctional enzyme aconitase is not only important in the citric acid cycle, but also functions as a key regulator of cell iron metabolism. Haem biosynthesis occurs partially in mitochondria as well as the biogenesis of iron-sulphur clusters that are co-factors in numerous iron-sulphur proteins. FRDA is characterised by a mutation of the frataxin gene, the protein of which serves as an iron chaperone in iron-sulphur cluster assembly. The lack of frataxin expression leads to defective iron-sulphur cluster biogenesis with decreased respiratory and aconitase activity. The resulting mitochondrial iron overload might fuel reactive oxygen species formation and contribute to clinical signs of oxidative stress. PD is typically associated with an increased iron content of the substantia nigra, the causes of which are largely unknown. Recent research demonstrated raised iron levels in individual dopaminergic neurons of the substantia nigra. Moreover, transferrin/transferrin receptor 2 mediated transport of iron into the mitochondria of these neurons was identified together with increased transferrin immunoreactivity. Resulting accumulation of iron into mitochondria might lead to oxidative stress damaging iron-sulphur cluster-containing proteins. Springer-Verlag, 2010 Iron nationallicence Mitochondria nationallicence Iron-sulphur cluster biogenesis nationallicence Friedreich ataxia nationallicence Parkinson disease nationallicence Gille Gabriele Klinik und Poliklinik für Neurologie, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany aut Reichmann Heinz Klinik und Poliklinik für Neurologie, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany aut Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 349-359 0300-9564 118:3<349 2011 118 702 https://doi.org/10.1007/s00702-010-0503-7 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0503-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gille Gabriele Klinik und Poliklinik für Neurologie, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany aut NATIONALLICENCE 700 1- Reichmann Heinz Klinik und Poliklinik für Neurologie, TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 349-359 0300-9564 118:3<349 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer