Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila

^*Department of Cell Biology, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129; ^†Faculté des Sciences d'Orsay, Université de Paris-Sud XI, 91405 Orsay, France; and ^‡Collège de France, 75231 Paris, France

Communicated by Walter J. Gehring, University of Basel, Basel, Switzerland, December 8, 2005 (received for review October 31, 2005)

Abstract

Deregulation of energy metabolism by external interventions or mutations in metabolic genes can extend lifespan in a wide range of species. We describe mutations in Drosophila melanogaster that confer resistance to oxidative stress and display a longevity phenotype. These phenotypes are associated with molecular lesions in a hitherto uncharacterized gene we named Enigma. We show that Enigma encodes a mitochondrial protein with homology to enzymes of the β-oxidation of fatty acids and that mutations in this locus affect lipid homeostasis. Our analysis provides further support to the notion that lipid metabolism may play a central role in metazoan lifespan regulation.

Footnotes

↵ § To whom correspondence should be addressed at: Department of Cell Biology, Harvard Medical School, Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129. E-mail: tsakonas{at}helix.mgh.harvard.edu.
Author contributions: P.M. and S.A.-T. designed research; P.M. performed research; P.M. and G.D.H. analyzed data; and P.M. and S.A.-T. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations: Egm, Enigma; ACAD, acyl-CoA dehydrogenase.
Data deposition: The microarray data have been deposited in Gene Expression Omnibus (accession no. GSE3566).