Lat1 is a Novel Metabolic Longevity Factor

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in yeast: CR needs Lat1, but Lat1 doesn't need CR or sirtuin

http://www.jbc.org/cgi/content/abstract/282/9/6161 (link for full text

pdf is below)

J. Biol. Chem., Vol. 282, Issue 9, 6161-6171, March 2, 2007

The Dihydrolipoamide Acetyltransferase Is a Novel Metabolic Longevity

Factor and Is Required for Calorie Restriction-mediated Life Span

Extension*

Calorie restriction (CR) extends life span in a wide variety of

species. Recent studies suggest that an increase in mitochondrial

metabolism mediates CR-induced life span extension. Here we present

evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2

component of the mitochondrial pyruvate dehydrogenase complex, is a

novel metabolic longevity factor in the CR pathway. Deleting the LAT1

gene abolishes life span extension induced by CR. Overexpressing Lat1

extends life span, and this life span extension is not further

increased by CR. Similar to CR, life span extension by Lat1

overexpression largely requires mitochondrial respiration, indicating

that mitochondrial metabolism plays an important role in CR.

Interestingly, Lat1 overexpression does not require the Sir2 family to

extend life span, suggesting that Lat1 mediates a branch of the CR

pathway that functions in parallel to the Sir2 family. Lat1 is also a

limiting longevity factor in nondividing cells in that overexpressing

Lat1 extends cell survival during prolonged culture at stationary

phase. Our studies suggest that Lat1 overexpression extends life span

by increasing metabolic fitness of the cell. CR may therefore also

extend life span and ameliorate age-associated diseases by increasing

metabolic fitness through regulating central metabolic enzymes.

full text is here: http://www.jbc.org/cgi/reprint/M607661200v1.pdf