Knockdown of mitochondrial heat shock protein 70 promotes progeria-like phenotypes in caenorhabditis elegans.
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.
Kimura
Kenji
K
Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan.
Tanaka
Nozomu
N
Nakamura
Nobuhiro
N
Takano
Syuichi
S
Ohkuma
Shoji
S
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D009866:Oogenesis / Q000235:genetics*; D010641:Phenotype; D011371:Progeria / Q000235:genetics / Q000378:metabolism
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate