Recent studies have propagated the model that the mitochondrial unfolded protein response (UPR^mt) is causal for lifespan extension from inhibition of the electron transport chain (ETC) in Caenorhabditis elegans. Here we report a genome-wide RNAi screen for negative regulators of the UPR^mt. Lifespan analysis of nineteen RNAi clones that induce the hsp-6_p::gfp reporter demonstrate differential effects on longevity. Deletion of atfs-1, which is required for induction of the UPR^mt, fails to prevent lifespan extension from knockdown of two genes identified in our screen or following knockdown of the ETC gene cco-1. RNAi knockdown of atfs-1 also has no effect on lifespan extension caused by mutation of the ETC gene isp-1. Constitutive activation of the UPR^mt by gain of function mutations in atfs-1 fails to extend lifespan. These observations identify several new factors that promote mitochondrial homoeostasis and demonstrate that the UPR^mt, as currently defined, is neither necessary nor sufficient for lifespan extension.