The nucleosome remodeling and deacetylase (NuRD) complex mediates the mitochondrial unfolded protein response and longevity in C. elegans

Mitochondrial stress during development causes widespread changes in chromatin structure to promote mitochondrial unfolded protein response (UPRmt), perpetuating an early response across a lifetime results in lifespan extension. We found that the nucleosome remodeling and deacetylase (NuRD) complex interact with the transcription factor DVE-1 to initiate the global chromatin condensation and induce the UPRmt in animals experienced with mild mitochondrial dysfunction. The condensed chromatin structure can be well maintained into later life that is beneficial for lifespan extension. Moreover, overexpression of the core component of the NuRD complex is sufficient to induce the UPRmt response and longevity in C. elegans. Thus, a transient mitochondrial stress response during early development is established and propagated into later life through the NuRD-dependent chromatin remodeling pathway to extend lifespan. Overall design: Comparison of gene expression changes in response to cco-1 RNAi treatment in N2 and lin-40(yth27) populations of C. elegans L4 animals