Inhibition of mitochondrial complex IV leads to secondary loss complex II-III activity: implications for the pathogenesis and treatment of mitochondrial encephalomyopathies

• Published in: Mitochondrion 2007-07, Vol.7 (4), p.284-287
• Main Authors: Hargreaves, I P, Duncan, A J, Wu, L, Agrawal, A, Land, J M, Heales, S J R
• Format: Article
• Language: English
• Subjects: Astrocytoma - metabolism; Cell Line; Citrate (si)-Synthase - metabolism; Coenzymes - metabolism; Electron Transport Complex II - metabolism; Electron Transport Complex III - metabolism; Electron Transport Complex IV - antagonists & inhibitors; Electron Transport Complex IV - metabolism; Glutathione - metabolism; Humans; Mitochondrial Encephalomyopathies - enzymology; Mitochondrial Encephalomyopathies - pathology; Mitochondrial Encephalomyopathies - therapy; Potassium Chloride - pharmacology; Protein Binding; Ubiquinone - analogs & derivatives; Ubiquinone - metabolism
• ISSN: 1567-7249
• DOI: 10.1016/j.mito.2007.02.001

Mitochondrial encephalomyopathies, arising from deficiencies of the electron transport chain (ETC) give rise to a wide clinical spectrum of presentation and are often progressive in nature. The aetiology of mitochondrial encephalomyopathies have yet to be fully elucidated, however, a successive loss of ETC function may contribute to the progressive nature of these disorders. The possibility arises that as a consequence of a primary impairment of ETC activity, secondary damage to the ETC may occur. In order to investigate this hypothesis, we established a model of cytochrome oxidase (Complex IV) deficiency in cultured human astrocytoma 1321N cells. Potassium cyanide (KCN, 1mM) resulted in a sustained 50% (p