Figure 4. mrp genes confer longevity effects through UPR^mt.

a, RNAi of mrp genes induced UPR^mt (hsp-6::GFP reporter), similar to cco-1 knockdown. Worms are synchronized at day 1 of adulthood. b, Quantification of UPR^mt upon knockdown of mrp or cco-1. (n=4) c, mrps-5 and cco-1, but not mev-1, RNAi, induce UPR^mt as reflected by the induction of HSP-6-GFP protein. d, Combined RNAi of mrps-5 and mev-1 synergistically increased UPR^mt, while combined cco-1/mrps-5 RNAi did not further increase UPR^mt (n=6). e, Knockdown of different mrp genes results in different levels of UPR^mt, which correlates with mean lifespan (n=33–61 worms for lifespan, n=3 for GFP). f–h, Epistasis with UPR^mt regulator haf-1. Double RNAi of mrps-5 and haf-1 partially prevented lifespan extension (f), UPR^mt (g, n=5), and reduction in respiration (h, n=10), compared to mrps-5 RNAi alone. i, In various tissues of mouse crosses, Ubl5, Abcb10 and Hspd1 expression correlated with Mrp expression. j, Hspd1 (HSP60) ties in a correlation network with Mrp and OXPHOS genes. Connecting lines indicate a Pearson correlation coefficient of 0.75–1.0. Bar graphs are mean±SEM, * p≤0.05; ** p≤0.01; *** p≤0.001. See also Supplementary Fig. 5–7 and Table 3.