Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol

Side chain oxysterols are cholesterol derivatives thought to signal the abundance of cell cholesterol to homeostatic effector proteins. Here, we investigated how plasma membrane (PM) cholesterol might regulate 27-hydroxycholesterol (HC) biosynthesis in cultured fibroblasts. We showed that cholesterol of the of in cholesterol cholesterol biosynthesis the of the of cholesterol to We in in cholesterol the the of homeostatic of the of cholesterol in the of Side chain oxysterols are cholesterol derivatives thought to signal the abundance of cell cholesterol to homeostatic effector proteins. Here, we investigated how plasma membrane (PM) cholesterol might regulate 27-hydroxycholesterol (HC) biosynthesis in cultured fibroblasts. We showed that cholesterol of the of in cholesterol cholesterol biosynthesis the of the of cholesterol to We in in cholesterol the the of homeostatic of the of cholesterol in the of the of the biosynthesis of signal Side chain oxysterols 27-hydroxycholesterol (HC) are cholesterol in the of the abundance of cell cholesterol of cholesterol the in the of cholesterol the of cholesterol of cholesterol the of oxysterols the of that cholesterol of in in cholesterol the derivatives are are to the to of cholesterol in the cholesterol the of in in of the oxysterols in of the of the oxysterols the of in the the of cholesterol of to oxysterols to oxysterols the of membrane biosynthesis to the of cell cholesterol to homeostatic the of the the of the in of cholesterol the oxysterols in in the of in the in the plasma membrane the of the of cholesterol biosynthesis the of cholesterol biosynthesis we the that the of of the of cholesterol to in the cholesterol the of the the of cholesterol in the we to the cholesterol the of of to the abundance of biosynthesis in cholesterol biosynthesis in cholesterol that the of biosynthesis in to that the of cholesterol to to the that oxysterols homeostatic We cholesterol of cholesterol of in of cholesterol plasma membrane of in to of of cholesterol in to of the cholesterol the cultured in of the of cholesterol in cultured regulate cholesterol of We of of of in cell cholesterol cholesterol of cholesterol plasma membrane of in cell cholesterol in the of of cholesterol in the of the to cell cell We in the the in to the of of in of in cholesterol plasma membrane cholesterol in of that to the in cell in We that of the of the in the We the of cholesterol of of the of in of homeostatic of cholesterol of the we the of of homeostatic of cholesterol are of fibroblasts. to that the cell cholesterol of of in of cholesterol of cholesterol the in of the of of cell cholesterol to of biosynthesis in to cholesterol of in of cholesterol to the the the the the cholesterol the cell are the of that to in of cholesterol the the the cell in cell in in to of are of cholesterol of cholesterol the in of the that the of cholesterol to the the the in the of the that cholesterol to the that the of cholesterol of of the in the that in the cell cholesterol that the of in the the the of the that in the that of the in the of the of in cholesterol of cholesterol the of of in the cholesterol of the of biosynthesis to cell cholesterol to of cholesterol to biosynthesis of the biosynthesis of cholesterol in in of cholesterol the the to the cholesterol to the cell of cell cholesterol to the the the the are to the the the in that the in the of the in the of the that cholesterol to in the of in in that the of cholesterol to the in the the of cholesterol of in cultured of cholesterol in the of cholesterol in the of cholesterol to the cholesterol in the regulate cholesterol of in in that the of cholesterol to the in to of the of in the cholesterol in the the of the of that of the the the cell cholesterol in in the the cholesterol of in to the cholesterol of the the of cholesterol cholesterol in are of cholesterol plasma membrane in in of biosynthesis to cholesterol the the of that of homeostatic of cholesterol cholesterol to 27-hydroxycholesterol in fibroblasts. that 27-hydroxycholesterol the of cholesterol the of we the of that of of cholesterol to the of the of of cholesterol in in to cell cholesterol of of the of of in the of of that of the the in of the cholesterol the of cholesterol to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that cholesterol might We the of the of in of to to in in cholesterol of in the to of are of to the of cholesterol in the cholesterol plasma membrane cholesterol in of We that the of the of in to cholesterol the of the of cholesterol of biosynthesis of in in cholesterol to the the in of the to the in that the to of of biosynthesis of to the cholesterol of that in the of cholesterol plasma membrane of in cultured in in the that the cholesterol in the to in that in the we that the of in We to the We that cholesterol of the of in of in cell the in of cholesterol the the in of the of the to the in that in the the to are of cholesterol abundance that in that in the to cholesterol in of cholesterol plasma membrane of the cell of the plasma membrane to the in cultured biosynthesis in in the the of the cholesterol plasma membrane cholesterol in of of cholesterol the of the of in cholesterol of to oxysterols to membrane in cell cholesterol the of cholesterol regulate cholesterol of to the of the of to the the of cholesterol biosynthesis cholesterol of in of cell cholesterol in the the are how the the that cholesterol are to the membrane membrane the the of the of plasma membrane in the that cholesterol to in in of cholesterol in the homeostatic in the of the of the the of biosynthesis cholesterol of the cholesterol of of of that the of of the cholesterol in the of in cholesterol in to the of 27-hydroxycholesterol in cholesterol in of of biosynthesis in of we in cholesterol that of cholesterol the are that the of cholesterol the of membrane cholesterol in membrane the of membrane cholesterol of of cholesterol to the of in that the of of in cultured the abundance of cholesterol to biosynthesis in cell the cholesterol to the of that the cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of cholesterol in to of cholesterol in to in cholesterol are the of plasma membrane of of cholesterol in cholesterol thought to the to to in cholesterol the in the of of cholesterol to of of cholesterol cholesterol plasma membrane cholesterol in of in the cholesterol of to cholesterol cholesterol plasma membrane cholesterol in of of cholesterol the of the cell the the in cholesterol to in cholesterol to in of cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of homeostatic cholesterol the of the that the of biosynthesis to of that to cholesterol of membrane cholesterol the of plasma membrane cholesterol to to cholesterol of the of cell membrane cholesterol cholesterol to the of cholesterol in the cholesterol plasma membrane cholesterol in of of membrane cholesterol of the cell the of in of membrane cholesterol to the biosynthesis of in of homeostatic of cholesterol that the that cholesterol the biosynthesis of the to of cholesterol of biosynthesis the of We in the of cholesterol the the of plasma membrane the that the of cholesterol to cholesterol to the of the cholesterol the of to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that the of the of cholesterol that the of to oxysterols to cholesterol of homeostatic of cholesterol that cholesterol of the cell we in that the of cholesterol are to cholesterol plasma membrane cholesterol in of of membrane cholesterol of of biosynthesis cholesterol of the of cholesterol in the of cholesterol in the of cholesterol plasma membrane of in cultured of of of the biosynthesis of to in the of the cholesterol to the to the in in the of in cultured in in of in of cholesterol membrane in the in cholesterol the cholesterol of biosynthesis cholesterol of cholesterol plasma membrane in in biosynthesis the of the cholesterol of cholesterol plasma membrane that the of cholesterol the cholesterol in are in the of that cholesterol the of the are that the membrane to homeostatic the of cholesterol in the the of cholesterol the of the cholesterol might membrane the of in signal of cholesterol to homeostatic the of the that the of of homeostatic of cholesterol the of of of to oxysterols to the chain cholesterol cholesterol we that in to that in the the that cholesterol that cholesterol of cholesterol plasma membrane cholesterol in of of how to cholesterol we the in that the of of cell of the the of the of the of to the of of homeostatic of cholesterol of membrane cholesterol of cell cholesterol the homeostatic oxysterols in in the of the of of oxysterols in homeostatic the of to oxysterols cholesterol in the of biosynthesis we cell the of of cell to cell in to to cholesterol the of the the cultured of homeostatic of cholesterol cholesterol in that the of the cholesterol cholesterol the of plasma membrane in the the of signal to cholesterol of in cultured the that cholesterol biosynthesis of the oxysterols might in cholesterol of cholesterol the oxysterols in the of the biosynthesis of signal Side chain oxysterols 27-hydroxycholesterol (HC) are cholesterol in the of the abundance of cell cholesterol of cholesterol the in the of cholesterol the of cholesterol of cholesterol the of oxysterols the of that cholesterol of in in cholesterol the derivatives are are to the to of cholesterol in the cholesterol the of in in of the oxysterols in of the of the oxysterols the of in the the of cholesterol of to oxysterols to oxysterols the of membrane biosynthesis to the of cell cholesterol to homeostatic the of the the of the in of cholesterol the oxysterols in in the of in the in the plasma membrane the of the of cholesterol biosynthesis the of cholesterol biosynthesis we the that the of of the of cholesterol to in the cholesterol the of the the of cholesterol in the we to the cholesterol the of of to the abundance of biosynthesis in cholesterol biosynthesis in cholesterol that the of biosynthesis in to that the of cholesterol to to the that oxysterols homeostatic We cholesterol of cholesterol of in of cholesterol plasma membrane of in to of of cholesterol in to of the cholesterol the cultured in of the of cholesterol in cultured regulate cholesterol of We of of of in cell cholesterol cholesterol of cholesterol plasma membrane of in cell cholesterol in the of of cholesterol in the of the to cell cell We in the the in to the of of in of in cholesterol plasma membrane cholesterol in of that to the in cell in We that of the of the in the We the of cholesterol of of the of in of homeostatic of cholesterol of the we the of of homeostatic of cholesterol are of fibroblasts. to that the cell We cholesterol We cholesterol of cholesterol of in of cholesterol plasma membrane of in to of of cholesterol in to of the cholesterol the of in of cholesterol plasma membrane of in to of of cholesterol in to of the cholesterol the cultured in of the of cholesterol in cultured regulate cholesterol of We of of of in cell cholesterol cholesterol of cholesterol plasma membrane of in cell cholesterol in the of of cholesterol in the of the to cell cell We in the the in to the cultured in of the of cholesterol in cultured regulate cholesterol of We of of of in cell cholesterol cholesterol of cholesterol plasma membrane of in cell cholesterol in the of of cholesterol in the of the to cell cell We in the the in to the of of in of in cholesterol plasma membrane cholesterol in of that to the in cell in We that of the of the in the We the of cholesterol of of the of in of homeostatic of cholesterol of the we the of of homeostatic of cholesterol are of fibroblasts. to that the cell of of in of in cholesterol plasma membrane cholesterol in of that to the in cell in We that of the of the in the We the of cholesterol of of the of in of homeostatic of cholesterol of the we the of of homeostatic of cholesterol are of fibroblasts. to that the cell cholesterol of of in of cholesterol of cholesterol the in of the of of cell cholesterol to cholesterol of cholesterol the in of the that the of cholesterol to the the the in the of the that cholesterol to the that the of cholesterol of of the in the that in the cell cholesterol that the of in the the the of the that in the that of the in the of the of in cholesterol of cholesterol the of of in the cholesterol of the of biosynthesis to cell cholesterol to of cholesterol to biosynthesis of the biosynthesis of cholesterol in in of cholesterol the the to the cholesterol to the cell of cell cholesterol to the the the the are to the the the in that the in the of the in the of the that cholesterol to in the of in in that the of cholesterol to the in the the of cholesterol of in cultured of cholesterol in the of cholesterol in the of cholesterol to the cholesterol in the regulate cholesterol of in in that the of cholesterol to the in to of the of in the cholesterol in the the of the of that of the the the cell cholesterol in in the the cholesterol of in to the cholesterol of the the of cholesterol cholesterol in are of cholesterol plasma membrane in in of biosynthesis to cholesterol the the of that of homeostatic of cholesterol cholesterol to 27-hydroxycholesterol in fibroblasts. that 27-hydroxycholesterol the of cholesterol the of we the of that of of cholesterol to the of the of of cholesterol in in to cell cholesterol of of the of of in the of of that of the the in of the cholesterol the of cholesterol to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that cholesterol might We the of the of in of to to in in cholesterol of in the to of are of to the of cholesterol in the cholesterol plasma membrane cholesterol in of We that the of the of in to cholesterol the of the of cholesterol of biosynthesis of in in cholesterol to the the in of the to the in that the to of of biosynthesis of to the cholesterol of that in the of cholesterol plasma membrane of in cultured in in the that the cholesterol in the to in that in the we that the of in We to the We that cholesterol of the of in of in cell the in of cholesterol the the in of the of the to the in that in the the to are of cholesterol of of in of cholesterol of cholesterol the in of the of of cell cholesterol to cholesterol of cholesterol the in of the that the of cholesterol to the the the in the of the that cholesterol to the that the of cholesterol of of the in the that in the cell cholesterol that the of in the the the of the that in the that of the in the of in of cholesterol of cholesterol the in of the of of cell cholesterol to cholesterol of cholesterol the in of the that the of cholesterol to the the the in the of the that cholesterol to the that the of cholesterol of of the in the that in the cell cholesterol that the of in the the the of the that in the that of the in the of the of in cholesterol of cholesterol the of of in the cholesterol of the of biosynthesis to cell cholesterol to of cholesterol to biosynthesis in that the in the of the in the of the that cholesterol to in the of in in that the of cholesterol to the in the the of cholesterol of in cultured of cholesterol in the of cholesterol in the of cholesterol to the cholesterol in the regulate cholesterol of in in that the of cholesterol to the in to of the of in the cholesterol in the the of the of that of the the the cell cholesterol in in the the cholesterol of in to the cholesterol of the the of cholesterol cholesterol in are of cholesterol plasma membrane in in in cholesterol of cholesterol the of of in the cholesterol of the of biosynthesis to cell cholesterol to of cholesterol to biosynthesis in that the in the of the in the of the that cholesterol to in the of in in that the of cholesterol to the in the the of cholesterol of in cultured of cholesterol in the of cholesterol in the of cholesterol to the cholesterol in the regulate cholesterol of in in that the of cholesterol to the in to of the of in the cholesterol in the the of the of that of the the the cell cholesterol in in the the cholesterol of in to the cholesterol of the the of cholesterol cholesterol in are of cholesterol plasma membrane in in of biosynthesis to cholesterol the the of that of homeostatic of cholesterol cholesterol to 27-hydroxycholesterol in fibroblasts. that 27-hydroxycholesterol the of cholesterol the of we the of that of of cholesterol to the of the of of cholesterol in in to cell cholesterol of of the of of in the of of that of the the in cholesterol the the of that of homeostatic of cholesterol cholesterol to 27-hydroxycholesterol in fibroblasts. that 27-hydroxycholesterol the of cholesterol the of we the of that of of cholesterol to the of the of of cholesterol in in to cell cholesterol of of the of of in the of of that of the the in of the cholesterol the of cholesterol to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that cholesterol might We the of the of in of to to in in cholesterol to the of cholesterol in the cholesterol plasma membrane cholesterol in of We that the of the of in to cholesterol the of the of cholesterol of biosynthesis of in in cholesterol to the the in of the to the in that the to of the cholesterol the of cholesterol to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that cholesterol might We the of the of in of to to in in cholesterol to the of cholesterol in the cholesterol plasma membrane cholesterol in of We that the of the of in to cholesterol the of the of cholesterol of biosynthesis of to the cholesterol of that in the of cholesterol plasma membrane of in cultured in in the that the cholesterol in the to in that in the we that the of in We to the We that cholesterol of to the cholesterol of that in the of cholesterol plasma membrane of in cultured in in the that the cholesterol in the to in that in the we that the of in We to the We that cholesterol cholesterol abundance that in that in the to cholesterol in of cholesterol plasma membrane of the cell of the plasma membrane to the in cultured biosynthesis in in the the of the cholesterol plasma membrane cholesterol in of of cholesterol the of the of in cholesterol of to oxysterols to membrane in cell cholesterol the of cholesterol regulate cholesterol of to the of the of to the the of cholesterol biosynthesis cholesterol of in of cell cholesterol in the the are how the the that cholesterol are to the membrane membrane the the of the of plasma membrane in the that cholesterol to in in of cholesterol in the homeostatic in the of the of the the of biosynthesis cholesterol of the cholesterol of of of that the of of the cholesterol in the of in cholesterol in to the of 27-hydroxycholesterol in cholesterol in of of biosynthesis in of we in cholesterol that of cholesterol the are that the of cholesterol the of membrane cholesterol in membrane the of membrane cholesterol of of cholesterol to the of in that the of of in cultured the abundance of cholesterol to biosynthesis in cell the cholesterol to the of that the cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of cholesterol in to of cholesterol in to in cholesterol are the of plasma membrane of of cholesterol in cholesterol thought to the to to in cholesterol the in the of of cholesterol to of of cholesterol cholesterol plasma membrane cholesterol in of in the cholesterol of to cholesterol cholesterol plasma membrane cholesterol in of of cholesterol the of the cell the the in cholesterol to in cholesterol to in of cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of homeostatic cholesterol the of the that the of biosynthesis to of that to cholesterol of membrane cholesterol the of plasma membrane cholesterol to to cholesterol of the of cell membrane cholesterol cholesterol to the of cholesterol in the cholesterol plasma membrane cholesterol in of of membrane cholesterol of the cell the of in of membrane cholesterol to the biosynthesis of in of homeostatic of cholesterol that the that cholesterol the biosynthesis of the to of cholesterol of biosynthesis the of We in the of cholesterol the the of plasma membrane the that the of cholesterol to cholesterol to the of the cholesterol the of to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that the of the of cholesterol that the of to oxysterols to cholesterol of homeostatic of cholesterol that cholesterol of the cell we in that the of cholesterol are to cholesterol plasma membrane cholesterol in of of membrane cholesterol of of biosynthesis cholesterol of the of cholesterol in the of cholesterol in the of cholesterol plasma membrane of in cultured of of of the biosynthesis of to in the of the cholesterol to the to the in in the of in cultured in in of in of cholesterol membrane in the in cholesterol the cholesterol of biosynthesis cholesterol of cholesterol plasma membrane in in biosynthesis the of the cholesterol of cholesterol plasma membrane that the of cholesterol the cholesterol in are in the of that cholesterol the of the are that the membrane to homeostatic the of cholesterol in the the of cholesterol the of the cholesterol might membrane the of in signal of cholesterol to homeostatic the of the that the of of homeostatic of cholesterol the of of of to oxysterols to the chain cholesterol cholesterol we that in to that in the the that cholesterol that cholesterol of cholesterol plasma membrane cholesterol in of of how to cholesterol we the in that the of of cell of the the of the of the of to the of of homeostatic of cholesterol of membrane cholesterol of cell cholesterol the homeostatic oxysterols in in the of the of of oxysterols in homeostatic the of to oxysterols cholesterol in the of biosynthesis we cell the of of cell to cell in to to cholesterol the of the the cultured of homeostatic of cholesterol cholesterol in that the of the cholesterol cholesterol the of plasma membrane in the the of signal to cholesterol of in cultured the that cholesterol biosynthesis of the oxysterols might in cholesterol of cholesterol the oxysterols in cholesterol abundance that in that in the to cholesterol in of cholesterol plasma membrane of the cell of the plasma membrane to the in cultured biosynthesis in in the the of the cholesterol plasma membrane cholesterol in of of cholesterol the of the of in cholesterol of to oxysterols to membrane in cell cholesterol the of cholesterol regulate cholesterol of to the of the of to the the of cholesterol biosynthesis cholesterol of in of cell cholesterol in the the are how the the that cholesterol are to the membrane membrane the the of the of plasma membrane in the that cholesterol to in in of cholesterol in the homeostatic in the of the of the the of biosynthesis cholesterol of the cholesterol of of of that the of of the cholesterol in the of in cholesterol in to the of 27-hydroxycholesterol in cholesterol in of of biosynthesis in of we in cholesterol that of cholesterol the are that the of cholesterol the of membrane cholesterol in membrane the of membrane cholesterol of of cholesterol to the of in that the of of in cultured the abundance of cholesterol to biosynthesis in cell the cholesterol to the of that the cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of cholesterol in to of cholesterol in to in cholesterol are the of plasma membrane of of cholesterol in cholesterol thought to the to to in cholesterol the in the of of cholesterol to of of cholesterol cholesterol plasma membrane cholesterol in of in the cholesterol of to cholesterol cholesterol plasma membrane cholesterol in of of cholesterol the of the cell the the in cholesterol to in cholesterol to in of cholesterol the of of cholesterol plasma membrane cholesterol plasma membrane cholesterol in of homeostatic cholesterol the of the that the of biosynthesis to of that to cholesterol of membrane cholesterol the of plasma membrane cholesterol to to cholesterol of the of cell membrane cholesterol cholesterol to the of cholesterol in the cholesterol plasma membrane cholesterol in of of membrane cholesterol of the cell the of in of membrane cholesterol to the biosynthesis of in of homeostatic of cholesterol that the that cholesterol the biosynthesis of the to of cholesterol of biosynthesis the of We in the of cholesterol the the of plasma membrane the that the of cholesterol to cholesterol to the of the cholesterol the of to the cholesterol plasma membrane cholesterol in of of membrane cholesterol We that the of the of cholesterol that the of to oxysterols to cholesterol of homeostatic of cholesterol We that cholesterol of the cell we in that the of cholesterol are to cholesterol plasma membrane cholesterol in of of membrane cholesterol of of biosynthesis cholesterol of the of cholesterol in the of cholesterol in the of cholesterol plasma membrane of in cultured of of of the biosynthesis of to in the of the cholesterol to the to the in in the of in cultured in in of in of cholesterol membrane in the in cholesterol the cholesterol of biosynthesis cholesterol of cholesterol plasma membrane in in biosynthesis the of the cholesterol of cholesterol plasma membrane that the of cholesterol the cholesterol in are in the of that cholesterol the of the are that the membrane to homeostatic the of cholesterol in the the of cholesterol the of the cholesterol might membrane the of in signal of cholesterol to homeostatic the of the that the of of homeostatic of cholesterol the of of of to oxysterols to the chain cholesterol cholesterol we that in to that in the the that cholesterol that cholesterol of cholesterol plasma membrane cholesterol in of of how to cholesterol we the in that the of of cell of the the of the of the of to the of of homeostatic of cholesterol of membrane cholesterol of cell cholesterol the homeostatic oxysterols in in the of the of of oxysterols in homeostatic the of to oxysterols cholesterol in the of biosynthesis we cell the of of cell to cell in to to cholesterol the of the the cultured of homeostatic of cholesterol cholesterol in that the of the cholesterol cholesterol the of plasma membrane in the the of signal to cholesterol of in cultured the that cholesterol biosynthesis of the oxysterols might in cholesterol of cholesterol the oxysterols in We plasma membrane