Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria

Citation
K. Hensley et al., Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria, CARCINOGENE, 21(5), 2000, pp. 983-989
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
21
Issue
5
Year of publication
2000
Pages
983 - 989
Database
ISI
SICI code
0143-3334(200005)21:5<983:DCRCCI>2.0.ZU;2-3
Abstract
Removal of choline from the diet results in accumulation of triglycerides i n the liver, and chronic dietary deficiency produces a non-genotoxic model of hepatocellular carcinoma. An early event in choline deficiency is the ap pearance of oxidized lipid, DNA and protein, suggesting that increased oxid ative stress may facilitate neoplasia in the choline deficient liver. In th is study, me find that mitochondria isolated from rats fed a choline-defici ent, L-amino acid defined diet (CDAA) demonstrate impaired respiratory func tion, particularly in regard to complex I-linked (NADH-dependent) respirati on. This impairment in mitochondrial electron transport occurs coincidental ly with alterations in phosphatidylcholine metabolism as indicated by an in creased ratio of long-chain to short-chain mitochondrial phosphatidylcholin e. Moreover, hydrogen peroxide (H2O2) generation is significantly increased in mitochondria isolated from CDAA rats compared with mitochondrial from n ormal rats, and the NADH-specific yield of H2O2 is increased by at least 2. 5-fold. These findings suggest an explanation for the rapid onset of oxidat ive stress and energy compromise in the choline deficiency model of hepatoc ellular carcinoma and indicate that dietary choline withdrawal may be a use ful paradigm for the study of mitochondrial pathophysiology in carcinogenes is.