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Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver

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Abstract

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-1α 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.

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Abbreviations

AIF:

Apoptosis inducing factor

AASA:

Aminoadipic semialdehyde in proteins

CEL:

Carboxyethyl-lysine in proteins

CML:

Carboxymethyl-lysine in proteins

DBI:

Double bond index

mtDNA:

Mitochondrial DNA

NRF-2:

nuclear respiratory factor-2

GSA:

Glutamic semialdehyde in proteins

MDAL:

Malondialdehyde-lysine in proteins

PGC-1α:

PPARγ Coactivator 1α

PI:

Peroxidizability index

ROS:

Reactive oxygen species

SAM:

S-Adenosylmethionine

SAH:

S-Adenosylhomocysteine

SIRT1:

Sirtuin 1

8-oxodG:

8-Oxo-7,8-dihydro-2′ deoxyguanosine

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Acknowledgments

This study was supported in part by I + D grants from the Spanish Ministry of Education and Science (BFU2006-14495/BFI), the Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad, RD06/0013/0012), the Generalitat of Catalunya (2005SGR00101), and “La Caixa” Foundation to R.P.; and from the Ministry of Education and Science (BFU2005-02584) and from CAM/UCM-GR74/07 (CCG07-UCM/BIO-2648) to G.B. P. Caro and J. Gómez received predoctoral fellowships from the Ministry of Education and Science.

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Authors and Affiliations

  1. Departamento de Fisiología Animal-II, Facultad de Ciencias Biológicas, Universidad Complutense, c/Jose Antonio Novais-2, Madrid, 28040, Spain

    Pilar Caro, Jose Gomez, Inés Sanchez, Ruben Garcia, Monica López-Torres & Gustavo Barja

  2. Department of Experimental Medicine, University of Lleida-IRBLLEIDA, Lleida, 25008, Spain

    Alba Naudí, Manuel Portero-Otin & Reinald Pamplona

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  1. Pilar Caro
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  2. Jose Gomez
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  3. Inés Sanchez
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  4. Ruben Garcia
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  9. Gustavo Barja
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Correspondence to Gustavo Barja.

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Caro, P., Gomez, J., Sanchez, I. et al. Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver. Biogerontology 10, 579–592 (2009). https://doi.org/10.1007/s10522-008-9200-4

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