STARD1 Functions in Mitochondrial Cholesterol Metabolism and Nascent HDL Formation. Gene Expression and Molecular mRNA Imaging Show Novel Splicing and a 1:1 Mitochondrial Association.

摘要: STARD1 moves cholesterol (CHOL) from the outer mitochondrial membrane (OMM) to inner (IMM) in steroidogenic cells. This activity is integrated into CHOL trafficking and synthesis homeostasis, involving uptake through SR-B1 LDL receptors distribution endosomes, ER, lipid droplets. In adrenal cells, imported matrix accompanied by delivery of several hundred molecules. transfer limits CYP11A1-mediated generation pregnenolone. coupled translation mRNA at OMM. testis slower seems be limiting. also functions a process ER OMM contacts. The START domain utilized family genes, which includes additional STARD (forms 3-6) GRAMD1B proteins that CHOL. forms 2 7 deliver phosphatidylcholine. STARD7 target their respective activities mitochondria, via N-terminal domains (NTD) over 50 amino acids. NTD not essential for steroidogenesis but exerts tissue-selective enhancement (testis>>adrenal). Three conserved sites cleavage processing protease (MPP) generate three forms, each potentially with specific functions, as demonstrated STARD7. expressed macrophage cardiac repair fibroblasts. Additional include metabolism CYP27A1 directs activation LXR export processes. generates 3.5- 1.6-kb alternative polyadenylation. 3.5-kb form exclusively binds PKA-induced regulator, TIS11b, extended 3'UTR control turnover. expression exhibits novel, slow splicing delayed mitochondria. Stimulation transcription PKA directed suppression SIK activate CRTC/CREB/CBP promoter complex. critical pulsatile hormonal vivo. sm-FISH RNA imaging shows flow single particles asymmetric accumulations primary transcripts gene loci 1:1 complex peri-nuclear Adrenal cells are similar distinguished appreciable basal prior activation. difference culture