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Carnitine transport by organic cation transporters and systemic carnitine deficiency
K Lahjouji1, G A Mitchell, I A Qureshi
1Division of Medical Genetics, Hôpital Sainte-Justine, 3175 Cote Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.
Abstract:
The intracellular homeostasis is controlled by different membrane transporters. Organic cation transporters function primarily in the elimination of cationic drugs, endogenous amines, and other xenobiotics in tissues such as the kidney, intestine, and liver. Among these molecules, carnitine is an endogenous amine which is an essential cofactor for mitochondrial beta-oxidation. Recently, a new family of transporters, named OCT (organic cation transporters) has been described. In this minireview, we present the recent knowledge about OCT and focus on carnitine transport, more particularly by the OCTN2. The importance of this sodium-dependent carnitine cotransporter, OCTN2, comes from various recently reported mutations in the gene which give rise to the primary systemic carnitine deficiency (SCD; OMIM 212140). The SCD is an autosomal recessive disorder of fatty acid oxidation characterized by skeletal myopathy, progressive cardiomyopathy, hypoglycemia and hyperammonemia. Most of the OCTN2 mutations identified in humans with SCD result in loss of carnitine transport function. Identifying these mutations will allow an easy targeting of the SCD syndrome. The characteristics of the juvenile visceral steatosis (jvs) mouse, an animal model of SCD showing similar symptoms as humans having this genetic disorder, are also described. These mice have a mutation in the gene encoding the mouse carnitine transporter octn2. Although various OCTN carnitine transporters have been identified and functionally characterized, their membrane localization and regulation are still unknown and must be investigated. This knowledge will also help in designing new drugs that regulate carnitine transport activity.
Insights
Organic cation transporters like OCTN2 are crucial for carnitine transport. Mutations in OCTN2 cause primary systemic carnitine deficiency, a serious metabolic disorder affecting fatty acid oxidation.
Area of Science:
- Cellular Biology
- Biochemistry
- Genetics
Background:
- Intracellular homeostasis relies on membrane transporters, including organic cation transporters (OCTs).
- Carnitine, an essential cofactor for mitochondrial beta-oxidation, is transported by OCTs.
- OCTN2 is a key sodium-dependent carnitine cotransporter.
Purpose of the Study:
- To review current knowledge on organic cation transporters (OCTs).
- To focus on carnitine transport by OCTN2.
- To discuss the implications of OCTN2 mutations in primary systemic carnitine deficiency (SCD).
Main Methods:
- Literature review of recent findings on OCTs and carnitine transport.
- Analysis of mutations in the OCTN2 gene associated with SCD.
- Description of the juvenile visceral steatosis (jvs) mouse model for SCD.
Main Results:
- Mutations in OCTN2 are a primary cause of SCD, leading to loss of carnitine transport function.
- The jvs mouse model exhibits symptoms similar to human SCD.
- Understanding OCTN2 mutations aids in targeting SCD.
Conclusions:
- OCTN2 mutations are central to primary systemic carnitine deficiency.
- Further research into OCTN transporter localization and regulation is needed.
- This knowledge can inform the development of novel therapeutic strategies for carnitine transport disorders.