Extended Data Fig. 10: Control experiment for Figs. 5 and 6.

a-d, Analysis of recombinant Lon protease (rLon) toxicity in healthy mice. a, b, C57BL/6 J WT mice were exposed to rLon intra-vesically for 12 days. No change in bladder weight or macroscopic appearance of the bladder was detected (n = 5 mice per group). Scale bar = 2 mm. c, Few genes were regulated in bladders from the rLon treated mice (n = 2 rLon, n = 1 Healthy control). d, MYC expression was not regulated but a small number of MYC-dependent genes was regulated in bladders from rLon treated healthy mice (32 activated, 1 inhibited). e-h, Analysis of per-oral rLon protease challenge in healthy C57BL/6 J WT mice, exposed to rLon per-orally twice daily for 14 days. f, No change in body weight, or macroscopic appearance of the intestine, liver, kidney or spleen was detected (n = 3 mice per group). Scale bar = 5 mm. g, Gene expression analysis detected a low number of regulated genes in intestinal segments of rLon treated mice (n = 3 rLon, n = 1 Healthy). h, MYC expression was not regulated and few MYC-related genes were affected after rLon challenge (1 activated, 8 inhibited genes) (FC compared to unchallenged controls, cut off FC ≥ 2, P < 0.05). Data are presented as mean ± s.d., N.S. = No significance.