XBX-6/TMBIM-2 deficiency suppressed the neuronal-to-intestinal UPR mt activation. (A) Representative photomicrographs demonstrating: bright-field images of aligned, wild-type (WT) animals. The area shown in white box is the region for imaging in Fig. 1(a); the expression pattern of the dve-1(zcIs39[dve-1p::dve-1::gfp]) reporter in WT day 2 adult animals (b); dve-1 reporter expression in neuronal EGL-20 (ythIs3[rgef-1p::egl-20 + myo-2p::tdtomato]) animals (c); neuronal EGL-20; tmbim-2(yth57) animals (d); intestinal EGL-20 (ythIs1[gly-19p::egl-20]) animals(e); intestinal EGL-20; tmbim-2(yth57) animals (f), respectively. The posterior region of the intestine where DVE-1::GFP is induced or suppressed is highlighted. (B) Quantification of the number of intestinal nuclei puncta with GFP signal per worm as shown in A. (C) A schematic diagram of three mutant alleles yth26, yth57, and yth130 of tmbim-2. (D) Representative photomicrographs demonstrating: dve-1 reporter expression in neuronal cox-5B knockdown (uthIs375[unc-119p::cox-5B HP; pRF(rol-6)]); sid-1(qt9) animals (a); neuronal cox-5B knockdown; sid-1(qt9); tmbim-2(yth130) animals (b); WT animals (c); and tmbim-2 (yth57)(d) grown on cox-5B RNAi from hatching. The posterior region of the intestine where DVE-1::GFP is induced or suppressed is highlighted. (E) Quantification of the number of intestinal nuclei puncta with GFP signal per worm as shown in D. (F) Representative photomicrographs demonstrating: the expression pattern of dve-1 reporter in WT animals expressing neuronal Q40 (rmIs110[rgef-1p::Q40::YFP](a); dve-1 reporter expression in tmbim-2 (yth57) animals expressing neuronal Q40 (b); intestinal rescue TMBIM-2 (ythEx289[gly-19p::tmbim-2])(c); pan-neuronal rescue TMBIM-2 (ythEx290[rgef-1p::tmbim-2])(d); ciliated-neuronal rescue TMBIM-2 (ythEx476[xbx-1p::tmbim-2])(e). The posterior region of the intestine where DVE-1::GFP is induced or suppressed is highlighted. (G) Quantification of the number of intestinal nuclei puncta with GFP signal per worm as shown in F. (H) Representative photomicrographs demonstrating: dve-1 reporter expression in tmbim-2 (yth57) animals expressing neuronal Q40::YFP (a); touch neurons rescue TMBIM-2 (ythEx568[mec-7p::tmbim-2])(b); NSM neurons rescue TMBIM-2 (ythEx772[tph-1(s)p::tmbim-2])(c); ADL neurons rescue TMBIM-2 (ythEx569[srh-220p::tmbim-2])(d); ADF/NSM neurons rescue TMBIM-2 (ythEx773[tph-1(l)p::tmbim-2])(e). The posterior region of the intestine where DVE-1::GFP is induced or suppressed is highlighted. (I) Quantification of the number of intestinal nuclei puncta with GFP signal per worm as shown in H. ***P < 0.001, ns denotes P > 0.05 via unpaired two-tailed Student’s t test. Error bars, SEM. n ≥ 15 worms. Scale bar, 250 μm.