Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver.
Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction. In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6-7 weeks, experimental parameters were measured in the liver. Amino acid restriction did not change the levels of the methionine metabolites S-adenosylmethionine and S-adenosylhomocysteine, mitochondrial oxygen consumption and ROS generation, oxidative damage to mtDNA, amounts of the respiratory complexes I-IV, and the mitochondrial biogenesis factors PGC-1alpha and NRF-2. On the other hand, adenylate energy charge, mitochondrial protein oxidation, lipooxidation and glycooxidation, the degree of mitochondrial fatty acid unsaturation, and the amount of the apoptosis inducing factor (AIF) were decreased in the RESTAAS group. Amino acid restriction also increased SIRT1 protein. These results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single aminoacid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification and AIF, and increases SIRT1, in rat liver.
Caro
Pilar
P
Departamento de Fisiología Animal-II, Universidad Complutense, Madrid, Spain. pcaromartin@bio.ucm.es
Gomez
Jose
J
Sanchez
Inés
I
Garcia
Ruben
R
López-Torres
Monica
M
Naudí
Alba
A
Portero-Otin
Manuel
M
Pamplona
Reinald
R
Barja
Gustavo
G
D000596:Amino Acids / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D004032:Diet; D004044:Dietary Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D051033:Apoptosis Inducing Factor; D004044:Dietary Proteins; D005227:Fatty Acids; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins