Abstract
The SLC25A20 transporter, also known as carnitine acyl-carnitine carrier (CAC), catalyzes the transport of short, medium and long carbon chain acyl-carnitines across the mitochondrial inner membrane in exchange for carnitine. The 30-year story of the protein responsible for this function started with its purification from rat liver mitochondria. Even though its 3D structure is not yet available, CAC is one of the most deeply characterized transport proteins of the inner mitochondrial membrane. Other than functional, kinetic and mechanistic data, post-translational modifications regulating the transport activity of CAC have been revealed. CAC interactions with drugs or xenobiotics relevant to human health and toxicology and the response of the carrier function to dietary compounds have been discovered. Exploiting combined approaches of site-directed mutagenesis with chemical targeting and bioinformatics, a large set of data on structure/function relationships have been obtained, giving novel information on the molecular mechanism of the transport catalyzed by this protein.
Highlights
The mitochondrial carnitine acyl-carnitine carrier (CAC) is the member A20 of the SLC25 protein family, including 53 solute transporters in humans [1,2,3], the majority of which are localized in the inner mitochondrial membrane
CAC is a key component of the carnitine shuttle [7], which is crucial for the mitochondrial β-oxidation pathway
The molecular basis of CAC substrate-binding and transport, as well as its regulation by post-translational modifications, have been explored using the site-directed mutagenesis approach complemented with bioinformatics and chemical targeting, together with parallel investigations in intact mitochondria to explore the physiological roles of these modifications
Summary
The mitochondrial carnitine acyl-carnitine carrier (CAC) is the member A20 of the SLC25 protein family, including 53 solute transporters in humans [1,2,3], the majority of which are localized in the inner mitochondrial membrane. Sequence identity acetylcarnitine with the human counterpart, most probably plays a acyl-carnitines different role, CACs, is to transport rather than mediumand long-chain that the transport[33,37]. Thisarticle, article,starting startingfrom fromsome somebasic basicinformation informationon onCAC, CAC, provides provides an an up-to-date up-to-date This comprehensive overview of the most recent discoveries about its molecular mechanism of comprehensive overview of the most recent discoveries about its molecular mechanism transport and the modulation/regulation of its transport function.
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