Electron transfer complexes of Ascaris suum muscle mitochondria: I. Characterization of NADH-cytochrome c reductase (complex I-III), with special reference to cytochrome localization

Takamiya, Shinzaburo; Furushima, Rieko; Okumura, Hiroshi

doi:10.1016/0166-6851(84)90107-5

Cited by 37 publications

(12 citation statements)

References 16 publications

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“…The enriched mitochondrial fractions of E. multilocularis protoscoleces were prepared essentially according to methods described previously for isolating adult Ascaris mitochondria (25,26). Briefly, the isolated protoscolex sediment was suspended in 5 volumes of mitochondrial preparation buffer (210 mM mannitol, 10 mM sucrose, 1 mM disodium EDTA, and 50 mM Tris-HCl [pH 7.5]) supplemented with 10 mM sodium malonate.…”

Section: Methodsmentioning

confidence: 99%

Anaerobic NADH-Fumarate Reductase System Is Predominant in the Respiratory Chain of Echinococcus multilocularis , Providing a Novel Target for the Chemotherapy of Alveolar Echinococcosis

Matsumoto

Sakamoto

Shinjyo

et al. 2008

Antimicrob Agents Chemother

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Alveolar echinococcosis, which is due to the massive growth of larval Echinococcus multilocularis, is a life-threatening parasitic zoonosis distributed widely across the northern hemisphere. Commercially available chemotherapeutic compounds have parasitostatic but not parasitocidal effects. Parasitic organisms use various energy metabolic pathways that differ greatly from those of their hosts and therefore could be promising targets for chemotherapy. The aim of this study was to characterize the mitochondrial respiratory chain of E. multilocularis, with the eventual goal of developing novel antiechinococcal compounds. Enzymatic analyses using enriched mitochondrial fractions from E. multilocularis protoscoleces revealed that the mitochondria exhibited NADH-fumarate reductase activity as the predominant enzyme activity, suggesting that the mitochondrial respiratory system of the parasite is highly adapted to anaerobic environments. High-performance liquid chromatography-mass spectrometry revealed that the primary quinone of the parasite mitochondria was rhodoquinone-10, which is commonly used as an electron mediator in anaerobic respiration by the NADH-fumarate reductase system of other eukaryotes. This also suggests that the mitochondria of E. multilocularis protoscoleces possess an anaerobic respiratory chain in which complex II of the parasite functions as a rhodoquinol-fumarate reductase. Furthermore, in vitro treatment assays using respiratory chain inhibitors against the NADH-quinone reductase activity of mitochondrial complex I demonstrated that they had a potent ability to kill protoscoleces. These results suggest that the mitochondrial respiratory chain of the parasite is a promising target for chemotherapy of alveolar echinococcosis.Echinococcosis is a near-cosmopolitan zoonosis caused by helminthic parasites belonging to the genus Echinococcus (family Taeniidae) (18). The life cycle of Echinococcus spp. includes an egg-producing adult stage in the definitive hosts and a larval stage in intermediate hosts including humans. The larval stage of the parasite produces a large number of infective protoscoleces that develop to adult worms after being ingested by the definitive host, or they produce a new parasite mass when liberated inside the intermediate host, causing metastases of the parasite lesions. The two major species of medical and public health importance are Echinococcus granulosus and E. multilocularis, which cause cystic echinococcosis and alveolar echinococcosis (AE), respectively.Human AE is a life-threatening disease, and without careful clinical management, it has a high fatality rate and poor prognosis. Humans acquire AE infection by ingesting eggs from adult parasitic worms. Early diagnosis and treatment (mainly by radical surgery) of human AE are difficult because the disease progresses slowly and usually takes more than several years before clinical symptoms become apparent. An efficient chemotherapeutic compound is still not available. The first choice for the chemotherapy of AE is benz...

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Section: Methodsmentioning

confidence: 99%

Anaerobic NADH-Fumarate Reductase System Is Predominant in the Respiratory Chain of Echinococcus multilocularis , Providing a Novel Target for the Chemotherapy of Alveolar Echinococcosis

Matsumoto

Sakamoto

Shinjyo

et al. 2008

Antimicrob Agents Chemother

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“…Complex II was purified from Ascaris mitochondria as described by Takamiya et al [3][4][5]. Purified complex II was treated with 20% (w/v) sodium dodecyl sulfate (SDS) and then subjected to gel chromatography on a Biogel P-60 (<400) column equilibrated with 2°70 (w/v) SDS [16].…”

Section: Purification Of the Fp Subunit From Ascaris Complex Hmentioning

confidence: 99%

“…We have isolated complex II from muscle mitochondria of adult worms of Ascaris [3][4][5][6], inhabitants of the host's small intestine where the oxygen 'supply is limited. Ascaris complex II, unlike its mammalian counterparts, functions physiologically as the terminal oxidase in the NADH-fumarate reductase system, an anaerobic respiratory chain [3,5].…”

Section: Introductionmentioning

confidence: 99%

Structural studies on three flavin‐interacting regions of the flavoprotein subunit of complex II in Ascaris suum mitochondria

et al. 1990

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The flavoprotein (Fp) subunit of mitochondrial complex II contains covalently bound FAD as a prosthetic group. In this study, the primary structure of the flavin-bound tryptic peptide from the Fp subunit of Ascaris complex II was determined and found to be highly similar to those of the corresponding flavin-binding regions of bovine heart and bacterial Fp subunits. Furthermore, the Ascaris Fp subunit was shown to contain two regions exhibiting striking sequence similarity to the segments that have been predicted to interact noncovalently with the AMP moiety of FAD in bacterial Fp subunits. The conservation of these two regions also in the mitochondrial Fp subunit suggests their functional importance.

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“…A terminal oxidase, cytochrome c oxidase (complex IV) is not detected in this respiratory chain system in adult, and the content of ubiquinol-cytochrome-c reductase (complex III) is also very low. 12) In contrast, in larvae which require oxygen for their development, the energy metabolism is aerobic. 13) When mitochondria were isolated from L3 larvae obtained by culturing fertilized eggs under aeration and biochemically investigated, the composition of the respiratory chain was almost the same as that in mammals as shown in Fig.…”

Section: I-1 Ascarid Life Cycle and Changes In Respiratory Chainmentioning

confidence: 99%

Parasite Mitochondria as a Target for Chemotherapy.

Kita

Miyadera

Saruta

et al. 2001

JOURNAL OF HEALTH SCIENCE

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The survival of parasites is dependent on that of the host. It is considered that parasites originated from nonparasitic ancestors and adapted to the environment in the host during the evolutional process, and developed hostand organ-specificities. Regarding energy metabolism, which is an essential factor for the survival, parasites adapt to the environment under a low oxygen tension in the host using metabolic systems which are very different from that of the host mammals. In such systems, parasite mitochondria play diverse roles. Especially, marked changes in the morphology and components of the mitochondria in the life cycle are very interesting in biological aspects such as developmental control and environmental adaptation. Such unique properties of parasite mitochondria could be promising targets for chemotherapy.

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Electron transfer complexes of Ascaris suum muscle mitochondria: I. Characterization of NADH-cytochrome c reductase (complex I-III), with special reference to cytochrome localization

Cited by 37 publications

References 16 publications

Anaerobic NADH-Fumarate Reductase System Is Predominant in the Respiratory Chain of Echinococcus multilocularis , Providing a Novel Target for the Chemotherapy of Alveolar Echinococcosis

Anaerobic NADH-Fumarate Reductase System Is Predominant in the Respiratory Chain of Echinococcus multilocularis , Providing a Novel Target for the Chemotherapy of Alveolar Echinococcosis

Structural studies on three flavin‐interacting regions of the flavoprotein subunit of complex II in Ascaris suum mitochondria

Parasite Mitochondria as a Target for Chemotherapy.

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