Figure 8 : MondoA and ChREBP knockdown compromise TFEB nuclear localization and target gene expression.

From: Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

Figure 8

(a) Representative fluorescent images of TFEB nuclear localization on control, MondoA or ChREBP knockdown in HeLa cells. Starvation-induced TFEB nuclear localization (4 h) is impaired by MondoA and ChREBP siRNA knockdown. (b) Quantification of TFEB nuclear localization on control or MondoA knockdown. (c) Quantification of TFEB nuclear localization on control or ChREBP knockdown. Bars indicate mean±s.e.m. from four biological replicates. χ2-test, **P<0.01 ***P<0.001 (b,c) (d) TFEB target gene expression is affected on MondoA and ChREBP knockdown. The bar represents mean±s.e.m. from five experiments relative to control siRNA 8-h growth condition. P-value (*P<0.05 and ***P<0.001) was determined by one-way analysis of variance (ANOVA) with Tukey’s test relative to control siRNA growth or starvation condition. (e) Representative western blotting showing that TFEB knockdown leads to decreased steady-state levels of MondoA and ChREBP. (f) A working model based on the current study. MML-1 is upregulated on germline removal. Activated MML-1/MXL-2 represses TOR activity by downregulating lars-1, leading to the nuclear localization of HLH-30. MML-1/MXL-2 also work downstream of TOR and activate preferential targets such as MDL-1, to regulate autophagy and longevity. HLH-30 also upregulates MML-1 through an unknown mechanism (see also Discussion). Scale bars, 50 μm (a).