A mitochondrial carnitine acylcarnitine translocase system

Area of Science:

• Mitochondrial biochemistry
• Metabolic regulation

Background:

• Carnitine plays a crucial role in fatty acid metabolism by transporting acyl groups across the mitochondrial inner membrane.
• Carnitine acetyltransferase (CAT) facilitates the reversible transfer of acetyl groups between carnitine and acetyl-CoA.

Purpose of the Study:

• To investigate the mechanism by which long chain acylcarnitines inhibit carnitine acetylation in heart mitochondria.
• To determine if the inhibition affects carnitine acetyltransferase activity directly or indirectly.

Main Methods:

• Studied the effect of long chain acylcarnitines on (-)carnitine acetylation coupled to pyruvate oxidation in heart mitochondria.
• Investigated carnitine and acylcarnitine transport across the mitochondrial membrane using [14-C]carnitine.
• Assessed the influence of temperature, substrate concentration, and stereospecificity on carnitine efflux.
• Quantified endogenous carnitine levels in mitochondria.

Main Results:

• Long chain acylcarnitines inhibited (-)carnitine acetylation but did not affect carnitine acetyltransferase activity.
• Mitochondria possess a saturable, temperature-dependent translocase system for carnitine and acylcarnitine exchange.
• This translocase system exhibited stereospecificity for acylcarnitines and was inhibited by long chain acyl(+)carnitines.
• Endogenous (-)carnitine was detected within mitochondria.

Conclusions:

• The inhibition of carnitine acetylation by long chain acylcarnitines is mediated by their interaction with a carnitine-acylcarnitine translocase system.
• This translocase system is responsible for the carnitine-dependent translocation of acyl groups across the mitochondrial inner membrane.