Gene expression profiling implicates OXPHOS complexes in lifespan extension of flies over-expressing a small mitochondrial chaperone, Hsp22.
Aging is a complex process accompanied by a decreased capacity to tolerate and respond to various stresses. Heat shock proteins as part of cell defense mechanisms are up-regulated following stress. In Drosophila, the mitochondrial Hsp22 is preferentially up-regulated in aged flies. Its over-expression results in an extension of lifespan and an increased resistance to stress. Hsp22 has chaperone-like activity in vitro, but the mechanism(s) by which it increases lifespan in flies are unknown. Genome-wide analysis was performed on long-lived Hsp22+ and control flies to unveil transcriptional changes brought by Hsp22. Transcriptomes obtained at 45days, 90% and 50% survival were then compared between them to focus more on genes up- or down-regulated in presence of higher levels of hsp22 mRNA. Hsp22+ flies display an up-regulation of genes mainly related to mitochondrial energy production and protein biosynthesis, two functions normally down-regulated during aging. Interestingly, among the 26 genes up-regulated in Hsp22+ flies, 7 genes encode for mitochondrial proteins, 5 of which being involved in OXPHOS complexes. Other genes that could influence aging such as CG5002, dGCC185 and GstS1 also displayed a regulation linked to Hsp22 expression. The up-regulation of genes of the OXPHOS system in Hsp22+ flies suggest that mitochondrial homeostasis is at the center of Hsp22 beneficial effects on lifespan.
Kim
Hyun-Ju
HJ
Laboratory of Cell and Developmental Genetics, Department of Medicine, PROTEO, Pav. C.E.-Marchand, Université Laval, 1030 Ave de la Médecine, Québec, Canada.
Morrow
Geneviève
G
Westwood
J Timothy
JT
Michaud
Sébastien
S
Tanguay
Robert M
RM
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D017344:Genes, Insect; D050259:Genes, Mitochondrial; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D015854:Up-Regulation
D017931:DNA Primers; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C490752:Hsp22 protein, Drosophila; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I