Similar to the UPRmt induced by cco-1 RNAi23, the LySR activated by vha-6 RNAi is also probably cell-non-autonomous in C. elegans, especially considering that vha-6 is predominantly expressed in the intestine while the aggregation-prone proteins in the Alzheimer’s disease, Huntington’s disease and ALS worm models applied in the current study were all expressed under the muscle-specific unc-54 promoter16,62,64,65. This evidence concerns the gene KARS1 and early-onset autosomal dominant Alzheimer disease.