Authors: Kimura K; Tanaka N; Nakamura N; Takano S; Ohkuma S
Abstract: Mitochondrial heat shock protein 70 (mthsp70) functions as a mitochondrial import motor and is essential in mitochondrial biogenesis and energy generation in eukaryotic cells. HSP-6 (hsp70F) is a nematode orthologue of mthsp70. Knockdown of HSP-6 by RNA interference in young adult nematodes caused a reduction in the levels of ATP-2, HSP-60 and CLK-1, leading to abnormal mitochondrial morphology and lower ATP levels. As a result, RNA interference-treated worms had lower motility, defects in oogenesis, earlier accumulation of autofluorescent material, and a shorter life span. These are the major phenotypes observed during the aging of worms, suggesting that the reduction of HSP-6 causes early aging or progeria-like phenotypes. The amount of HSP-6 became dramatically reduced at the expected mean life span in not only wild-type but also in long and short life span mutant worms (wild-type, daf-2, and daf-16). Mitochondrial HSP-60 and ATP-2 were also reduced following the reduction of HSP-6 during aging. These results suggest that the reduction of HSP-6 causes defects in mitochondrial function at the final stage of aging, leading to mortality.Keywords: Adenosine Triphosphate/biosynthesis; Animals; Animals, Genetically Modified; Caenorhabditis elegans/cytology/*genetics/metabolism; Caenorhabditis elegans Proteins/biosynthesis/genetics; Chaperonin 60/biosynthesis/genetics; Female; HSP70 Heat-Shock Proteins/*deficiency/metabolism; Humans; Longevity/*genetics; Male; Mitochondria/metabolism/pathology; Mitochondrial Proteins/*deficiency/metabolism; Motor Activity/genetics; Oogenesis/*genetics; Phenotype; Progeria/genetics/metabolism
Journal: The Journal of biological chemistry
Date: Dec. 26, 2006
Select reference article to upload
Kimura K, Tanaka N, Nakamura N, Takano S, Ohkuma S (2007) Knockdown of mitochondrial heat shock protein 70 promotes progeria-like phenotypes in caenorhabditis elegans. The Journal of biological chemistry 282: 5910-8.