Disproportionate Deficiency of Iron-Sulfur Clusters and Subunits of Complex I in Mitochondrial Encephalomyopathy

Abstract

ABSTRACT: To investigate the molecular abnormality in the mitochondria from various tissues of an autopsied patient exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, we have examined the enzymatic activity, iron-sulfur cluster, and subunit composition of the NADH-ubiquinone oxidoreductase (complex I). Rotenone-sensitive NADH-cytochrome c reductase activity was found to be decreased in all the tissues examined. A detailed study of the liver mitochondria has shown that NADH-ubiquinone oxidoreductase activity was greatly diminished. Analysis of the electron paramagnetic resonance spectra of the liver submitochondrial particles revealed a disproportionate deficiency of iron-sulfur clusters in the complex I segment of the respiratory chain. Signals from the clusters N-2 and N-3 diminished more drastically than those from clusters N-1b and N-4. Immunoblotting analysis showed that the 75-kD, 51- kD, and several other subunits were markedly diminished among multiple subunit polypeptides of complex I. These findings suggest that the underlying bases for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are defects, at least, in the complex I subunits containing a flavin and/or iron-sulfur cluster(s), which resulted in deficiencies of some iron-sulfur clusters.

DOI: 10.1203/00006450-198902000-00023

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@article{Ichiki1989DisproportionateDO, title={Disproportionate Deficiency of Iron-Sulfur Clusters and Subunits of Complex I in Mitochondrial Encephalomyopathy}, author={Takashi Ichiki and Masashi Tanaka and Masanori Kobayashi and Naruji Sugiyama and Hiroshi Suzuki and Morimitsu Nishikimi and Tomoko Ohnishi and Ikuya Nonaka and Yoshiro Wada and Takayuki Ozawa}, journal={Pediatric Research}, year={1989}, volume={25}, pages={194-201} }