Cholate extracts of mitochondrial outer membranes increase inhibition by malonyl-CoA of carnitine palmitoyltransferase-I by a mechanism involving phospholipids

R. L. Mynatt, J. J. Greenhaw, George Cook

Research output: Contribution to journalArticle

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Abstract

It has been reported that sodium cholate can separate the catalytic component of carnitine palmitoyltransferase-I (CPT-I) from a putative malonyl-CoA-binding regulatory protein capable of conferring sensitivity to malonyl-CoA on CPT-II. We found that cholate preferentially extracted a contaminating malonyl-CoA-sensitive CPT from mitochondrial inner membranes. When cholate extracts of outer membranes were incubated either with cholate extracts of inner membranes or with osmotically swollen mitochondria, inhibition of CPT by malonyl-CoA was increased. Treatment of intact mitochondria with subtilisin abolished the increased inhibition by malonyl-CoA, suggesting that the outer-membrane CPT-I was responsible for the increased inhibition. Incubation of cholate extracts with proteinase K did not prevent the increased inhibition. Fractionation of the cholate extract indicated the presence of phospholipids. Addition of cardiolipin or phosphatidylglycerol to osmotically swollen mitochondria increased sensitivity of CPT to malonyl-CoA, but several other phospholipids did not. When cardiolipin was added to intact mitochondria from either starved or fed rats, there were large increases in inhibition by malonyl-CoA; sensitivity in mitochondria from starved rats increased to that normally observed with mitochondria from fed rats. These results suggest that phospholipids are responsible for the increased inhibition of CPT by malonyl-CoA with added cholate extracts and that changes in membrane composition may be involved in the physiological regulation of CPT-I.

Original languageEnglish (US)
Pages (from-to)761-767
Number of pages7
JournalBiochemical Journal
Volume299
Issue number3
DOIs
StatePublished - Jan 1 1994

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Cholates
Malonyl Coenzyme A
Carnitine O-Palmitoyltransferase
Mitochondrial Membranes
Mitochondria
Phospholipids
Membranes
Rats
Cardiolipins
Sodium Cholate
Subtilisin
Endopeptidase K
Phosphatidylglycerols
Fractionation
Carrier Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cholate extracts of mitochondrial outer membranes increase inhibition by malonyl-CoA of carnitine palmitoyltransferase-I by a mechanism involving phospholipids. / Mynatt, R. L.; Greenhaw, J. J.; Cook, George.

In: Biochemical Journal, Vol. 299, No. 3, 01.01.1994, p. 761-767.

Research output: Contribution to journalArticle

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