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. 2014 Jan 16;124(2):768–784. doi: 10.1172/JCI69413

Figure 8. LRP130-7KR stimulates mitochondrial transcription and promotes OXPHOS.

Figure 8

(A) LRP130-7KR, which mimics deacetylated protein, showed increased affinity for aas 1–710 of POLRMT, a fragment that contains the catalytic domain. See Supplemental Figure 10 for more detailed mapping. (B) In contrast, compared with LRP130-WT, LRP130-7KR showed no differential affinity for TFB2M. (C, D, and F) Using 293T cells, endogenous human LRP130 was knocked down >95%, then reconstituted with murine LRP130-WT or LRP130-7KR (see Supplemental Figure 11). The shRNA targeting human LRP130 does not target mouse Lrp130 (not shown). Endogenous NAD+-dependent sirtuin activity was inhibited with 10 mM nicotinamide for 16 hours. LRP130-7KR had greater (C) mitochondrially encoded gene expression (n = 3), (D) mitochondrial transcription (n = 3), and (F) maximal respiration (n = 5) versus LRP130-WT. (E) Immunoblot showing similar levels of ectopically expressed LRP130-WT and LRP130-7KR. See Supplemental Figure 11 for total LRP130 protein. Data are mean ± SEM. *P < 0.05, ***P < 0.001, 2-way ANOVA (C and D) or 2-tailed unpaired Student’s t test (F).