Abstract
L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.
Highlights
Biological processes involved in the regulation of energy metabolism are highly conserved in all living organisms
L-carnitine plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration
Carnitine acyltransferases are grouped in different classes based on their specificity for the length of the fatty acyl group used as a substrate: (1) Carnitine acetyltransferase (CrAT or CAT) uses acetyl-coenzyme A (CoA) as a substrate [2]; (2) Carnitine octanoyltransferase (CrOT or COT) regulates the peroxisomal metabolism of Very-Long-Chain Fatty Acids (VLCFA) and branched-chain fatty acids by promoting the transport of medium-length acyl (C8–C10) from peroxisomes to mitochondria for further breakdown [3,4]; (3) Carnitine palmitoyltransferase (CPTs) 1 and 2 are enzymes located on the outer and inner mitochondrial membrane, respectively, and are responsible for delivering Long-Chain Fatty Acids (LCFA) (C16–C20) into the mitochondrial matrix where they enter β-oxidation [1,5]
Summary
Biological processes involved in the regulation of energy metabolism are highly conserved in all living organisms. L-Carnitine plays a key role in lipid metabolism by transporting fatty acids into the mitochondria of the cell where they are converted into energy. The key role played by L-carnitine in energy production is highly conserved across organisms; the study of the mechanisms linking β-oxidation and L-carnitine to neurodegenerative disorders could be facilitated in simpler animal models, such as the fruit fly Drosophila melanogaster [40]. Mmeellaannooggaasstteerr;; hhoowweevveerr,, tthhee pprreesseennccee ooff ppuuttaattiivvee oorrtthhoollooggss ooff tthhee ccaarrnniittiinnee bbiioossyynntthheessiiss ggeenneess iinn iittss ggeennoommee lleettss uuss assume that, like humans, Drosophila can biosynthesize L-carnitine. There is no experimental evidence that these genes participate in the L-carnitine biosynthetic pathway
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