YAO Xiuping,CHEN Sixi,REN Yaguang, et al. Mfn-1 RNAi activates the mitochondrial unfolded protein response via the ATFS-1 mediated pathway in C. elegans[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2014, 44(6): 391-394.
Abstract：Objective: To research the effect of mfn-1 RNAi on mitochondrial unfolded protein response and its mechanism. Methods: Worm strains SJ4058 and SJ4100(mitochondrial unfolded protein response reporter), TJ375 (cytosolic unfolded protein response reporter), and SJ4005 (endoplasmic reticulum unfolded protein response reporter) were treated by mfn-1 RNAi, and to observe whether the corresponding chaperones were activated or not; crossing strain SJ4058 into haf-1 gene loss of function strain RB867 and atfs-1 gene loss of function strain VC3201 respectively, the obtained homozygous animals were treated by mfn-1 RNAi, and their progenies were observed for fluorescence to explore whether the activation of chaperones was relied on HAF-1 or ATFS-1. Results: Mfn-1 RNAi specifically activated the mitochondria specific chaperones HSP-6 and HSP-60, but not cytosol specific chaperon HSP-16.2 and endoplasmic reticulum specific chaperon HSP-4; We obtained the hsp-60::gfp/atfs-1(gk3094) V and hsp-60::gfp/haf-1(ok705)IV strains by crossing and their genotypes were confirmed by PCR. The two strains were treated by mfn-1 RNAi, and further studies showed that the activation of chaperon HSP-60 was relied on ATFS-1 rather than HAF-1. Conclusion: Mfn-1 RNAi treatment specifically activated mitochondrial rather than cytosolic and endoplasmic reticulum unfolded protein response, suggesting the mitochondria proteostasis is affected, but that of cytosol and endoplasmic reticulum are not; the activation of mitochondrial unfolded protein response by mfn-1 RNAi is dependent on the transcription factor ATFS-1, not the mitochondria membrane protein HAF-1.
