Figure 2.

Chemical inhibition of Sirt1 impairs UPR^mt activation in injured larval fins

(A) Heatmap of relative gene expression levels derived from the transcriptional profiling data demonstrates that previously studied regeneration genes (top half) as well as the UPR^mt genes (bottom half) are all up-regulated in the injured fins during regeneration.

(B) GSEA indicates that mitochondrial translation and transcription are among the cellular processes that are most enhanced during fin regeneration.

(C) qRT-PCR assays show that the expression of two mitochondrial transcriptional machinery components, polrmt and tf2bm, are enhanced in zebrafish adult fins during regeneration.

(D) The schematic depicts the mechanism of Sirt1 inhibition by various small molecule inhibitors used in subsequent experiments.

(E) Representative images of hspd1 in situ hybridization.

(F) qRT-PCR assays show that Sirt1 inhibition via Sirtinol treatment or Nampt inhibition via FK866 treatment suppresses the UPR^mt gene expression in the injured larval fin. (Error bars indicate standard deviation. Student’s t test was performed to determine statistical significance. ∗p < 0.05.)