Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism.

摘要: The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved intracellular trafficking of lipids. Sixteen mammalian START domain-containing proteins have been to date. StAR, a targeted mitochondria, stimulates movement cholesterol from outer inner mitochondrial membranes, where it metabolized into pregnenolone cells. MLN64, domain most closely related localized late endosomes along with other sterol trafficking, including NPC1 and NPC2, has postulated participate distribution membranes. To investigate role MLN64 metabolism, we created mice mutation Mln64 expecting find phenotype similar that humans lacking or NPC2 (progressive neurodegenerative symptoms, free accumulation lysosomes). Unexpectedly, homozygous for mutant allele were viable, neurologically intact, fertile. No significant alterations plasma levels, liver content distribution, expression genes metabolism observed, except an increase ester storage fed high fat diet. Embryonic fibroblast cells transfected side-chain cleavage system primary cultures granulosa showed defects as reflected reduced conversion endogenous steroid hormones. These observations suggest largely dispensable mice.