Effect of the lipophilic o-naphthoquinone CG 10-248 on rat liver mitochondria structure and function.
CG 10-248 (3,4-dihydro-2,2 dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione), a beta-lapachone analogue, modified the ultrastructure of rat liver mitochondria in vitro, in the absence of added oxidizable substrates. The condensed mitochondrial state was replaced by the orthodox or swollen state to a significant degree. The number of modified mitochondria depended on incubation time and quinone concentration, in the 25-100 microM range. Under the same experimental conditions, mitochondrial respiration was uncoupled as indicated by the increase in the rate of succinate oxidation by controlled mitochondria in metabolic state "4" (not in state "3"), and by the activation of latent F0F1-ATP synthase. Taking into account structural similarities, the results reported here may be valid for other o-naphthoquinones, such as beta-lapachone.
Lopez
Lidia M
LM
Department of Cell Biology and Neurosciences, School of Medicine, University of Buenos Aires.
Pellegrino de Iraldi
Amanda
A
Carrizo
Patricia H
PH
Dubin
Marta
M
Stoppani
Andrés O M
AO
D000818:Animals; D006868:Hydrolysis; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000648:ultrastructure; D009285:Naphthoquinones / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013997:Time Factors
D009285:Naphthoquinones; D011809:Quinones; C014638:beta-lapachone; D006180:Proton-Translocating ATPases; D010100:Oxygen