Detoxification of reactive aldehydes in mitochondria: effects of age and dietary restriction.
Previously, we proposed that reactive aldehydic products generated from lipid peroxidation might be the deleterious cause of mitochondrial dysfunction during aging. Our present study focuses on the roles that aging and dietary restriction (DR) play in the elimination of 4-hydroxynonenal (HNE) in rat liver by exploring three enzymatic systems: aldehyde dehydrogenase (ALDH), glutathione S-transferase (GST), and alcohol dehydrogenase (ADH). Results show that the main pathways of HNE elimination in mitochondria are through ALDH-catalyzed oxidation, and the GST-catalyzed conjugation of HNE. Findings also show that age reduces both ALDH and GST activities; mitochondrial HNE oxidation by ALDH declines at 18 and 24 months of age, and the glutathione conjugation of HNE reduces at 24 months of age. However, these enzymatic processes were found to be well-preserved in DR animals throughout their life span, supporting the evidence of less HNE accumulation in the membranes of restricted rats. These findings are consistent with our earlier proposal that indicates an age-associated decrease in mitochondrial detoxification as a major underlying process for malondialdehyde and lipofuscin accumulation in older animals. They also indicate that the prevention of the age-associated decrease in aldehyde detoxification by DR may be an important mechanism underlying enhanced aldehyde elimination, thus minimizing the functional deterioration observed in mitochondria of old animals.
Chen
J J
JJ
Department of Physiology, University of Texas Health Science Center at San Antonio 78284-7756, USA.
Yu
B P
BP
D000375:Aging / Q000502:physiology*; D000426:Alcohol Dehydrogenase / Q000032:analysis / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D004032:Diet; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000447:Aldehydes; D009243:NAD; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase; D005978:Glutathione