A mitochondrial UPR-independent role of DVE-1 in longevity regulation

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 targeted exploration of downstream factors contributing to the prolonged lifespan observed in sensory ciliary mutants, we discovered that DVE-1 plays a crucial role in facilitating the longevity conferred by these mutants. Intriguingly, this effect is independent of mitoUPR, the canonical function of DVE-1. Furthermore, our investigations unveiled that DVE-1 also participates in extending lifespan under the influence of dietary restriction and germline signaling, again distinct from its role in mitoUPR. Thus, our findings shed light on a novel mitoUPR-independent function of DVE-1 in regulating lifespan. Mechanistically, while mitochondrial stress typically prompts nuclear accumulation of DVE-1 to initiate the transcriptional mitoUPR program, the long-lived daf-10 sensory ciliary mutant facilitates the cytosolic translocation of DVE-1. This observation suggests a cytosolic role for DVE-1 in lifespan extension. Overall, our study implies that, in contrast to the more narrowly defined role of the mitoUPR-related transcription factor ATFS-1, the transcriptional regulator DVE-1 may possess broader functions than previously recognized in modulating longevity and defending against stress.