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The mitoUPR transcription factor ATFS-1 is not involved in ciliary modulation of longevity (A) Illustration of signaling pathways required for mitoUPR activation in C. elegans. Among them, two parallel pathways are centered around two transcription factors/regulators, ATFS-1 and DVE-1, both of which are highlighted in blue. (B-I) atfs-1 RNAi has no significant impacts on the lifespans of WT (B) and daf-10(p821) (C), osm-1(p808) (D), dyf-1(mn335) (E), osm-3(p802) (F), xbx-1(ok279) (G), klp-11(tm324) (H), and osm-12(n1606) (I) mutant worms.
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The special AT-rich sequence-binding (SATB) protein DVE-1 is widely recognized for its pivotal involvement in orchestrating the retrograde mitochondrial unfolded protein response (mitoUPR) in C. elegans. In our study of downstream factors contributing to lifespan extension in sensory ciliary mutants, we find that DVE-1 is crucial for this longevity...
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... does DVE-1 regulate lifespan downstream of ciliary mutations? As the primary known function of DVE-1 is to mediate mitoUPR in a pathway parallel to that of ATFS-1 ( Figure 3A), we explored whether ATFS-1 might also participate in the downstream effects of ciliary modulation on longevity. Employing a similar approach to our investigation of DVE-1, we administered atfs-1 RNAi to both WT and various ciliary mutant worms. ...
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... a similar approach to our investigation of DVE-1, we administered atfs-1 RNAi to both WT and various ciliary mutant worms. Consistent with prior studies, 41,42 genetic disruption of atfs-1 had no significant impact on the lifespan of WT worms ( Figure 3B). Moreover, we observed that atfs-1 RNAi did not alter the lifespans of any of the ciliary mutants examined (Figures 3C-3I). ...
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... with prior studies, 41,42 genetic disruption of atfs-1 had no significant impact on the lifespan of WT worms ( Figure 3B). Moreover, we observed that atfs-1 RNAi did not alter the lifespans of any of the ciliary mutants examined (Figures 3C-3I). Thus, unlike DVE-1, ATFS-1 does not play a significant role in ciliary modulation of longevity. ...
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... we did not detect induction of hsp-6 expression, a well-established marker for mitoUPR activation, 27,35 in the long-lived daf-10(p821), normal-lifespan klp-11(tm324), or short-lived osm-12(n1606) mutant backgrounds ( Figure 4A). Furthermore, we explored the potential impact of other key mitoUPR regulators known to function alongside DVE-1, including LIN-65, MET-2, UBL-5, and CLPP-1 ( Figure 3A). 23,27 To our surprise, RNAi targeting these mitoUPR regulators did not suppress the longevity conferred by ciliary mutations as effectively as dve-1 RNAi (Figures 4C-4G). ...
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... In line with these findings, we observed increased levels of nuclear DVE-1::GFP (Figures 5C and 5D) following spg-7 RNAi treatment, as indicated by the zcIs39[Pdve-1::dve-1::gfp] translational reporter line. 28 Although DVE-1::GFP fluorescence is readily detectable in various head neurons and posterior intestinal cells ( Figure S3A), the larger and more distinct cells of the posterior intestine make it much easier to observe and quantify nuclear localization. In addition, our tissue-specific RNAi experiment suggested that DVE-1 primarily regulates the lifespan through its function in the intestine rather than neurons ( Figure S1). ...
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... we observed much-reduced nuclear accumulation of DVE-1::GFP in the daf-10(p821) mutant ( Figure 5G). Despite this, the total fluorescence signal of DVE-1::GFP was actually higher in daf-10(p821) mutants ( Figures 5G and S3A), suggesting that the daf-10(p821) mutant does not reduce the total expression level of DVE-1. ...
