The mitochondrial carnitine/acylcarnitine carrier: Function, structure and physiopathology

Indiveri, Cesare; Iacobazzi, Vito; Tonazzi, Annamaria; Giangregorio, Nicola; Infantino, Vittoria; Convertini, Paolo; Console, Lara; Palmieri, Ferdinando

doi:10.1016/j.mam.2011.10.008

Cited by 217 publications

(194 citation statements)

References 76 publications

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“…In contrast to the great majority of mitochondrial carriers, which are obligatory exchangers (31-37), SLC25A29 catalyzes a substantial uniport besides exchange of substrates. In this respect, SLC25A29 resembles the carriers for phosphate (38), glutamate (39), and carnitine/acylcarnitine (40), which are also capable of mediating uniport. All these carriers, including SLC25A29, operate exchanges in vitro at a much higher rate than uniports (from 2.8-to 10-fold higher).…”

Section: Discussionmentioning

confidence: 99%

The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids

Porcelli

Fiermonte

Longo

et al. 2014

Journal of Biological Chemistry

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Background: SLC25A29 encoded by the human SLC25A29 gene was suggested to be a mitochondrial carnitine/acylcarnitine-or ornithine-like transporter. Results: The recombinant, purified SLC25A29 transports arginine, lysine, and to a lesser extent ornithine and histidine but not carnitine and acylcarnitines. Conclusion: SLC25A29 is a mitochondrial transporter for basic amino acids. Significance: Another member of the mitochondrial carrier superfamily responsible for 12 monogenic diseases has been thoroughly characterized.

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Section: Discussionmentioning

confidence: 99%

The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids

Porcelli

Fiermonte

Longo

et al. 2014

Journal of Biological Chemistry

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“…Partially based on previously published models (7,46). trix, where fatty acid ␤-oxidation takes place (24). Despite this crucial role in the generation of energy in muscle, little is known about the effects of deconditioning and exercise on SLC25A20 expression levels.…”

Section: Discussionmentioning

confidence: 99%

Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle

Lammers

Poelkens

Duijnhoven

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Lammers G, Poelkens F, van Duijnhoven NT, Pardoel EM, Hoenderop JG, Thijssen DH, Hopman MT. Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle. Am J Physiol Endocrinol Metab 303: E1245-E1251, 2012. First published October 9, 2012; doi:10.1152/ajpendo.00356.2012.-Physical deconditioning is associated with the development of chronic diseases, including type 2 diabetes and cardiovascular disease. Exercise training effectively counteracts these developments, but the underlying mechanisms are largely unknown. To gain more insight into these mechanisms, muscular gene expression levels were assessed after physical deconditioning and after exercise training of the lower limbs in humans by use of gene expression microarrays. To exclude systemic effects, we used human models for local physical inactivity (3 wk of unilateral limb suspension) and for local exercise training (6 wk of functional electrical stimulation exercise of the extremely deconditioned legs of individuals with a spinal cord injury). The most interesting subset of genes, those downregulated after deconditioning as well as upregulated after exercise training, contained 18 genes related to both the "insulin action" and "adipocytokine signaling" pathway. Of these genes, the three with strongest up/downregulation were the muscular fatty acid-binding protein-3 (FABP3), the fatty acid oxidizing enzyme hydroxyacyl-CoA dehydrogenase (HADH), and the mitochondrial fatty acid transporter solute carrier 25 family member A20 (SLC25A20). The expression levels of these genes were confirmed using RT-qPCR. The results of the present study indicate an important role for a decreased transport and metabolism of fatty acids, which provides a link between physical activity levels and insulin signaling.transcriptome; microarray; fatty acid metabolism; insulin resistance THE HUMAN GENOME HAS EVOLVED on the basis of a physically active lifestyle, but our society has become increasingly sedentary. Physical inactivity has detrimental health consequences, including the development of insulin resistance and eventually type 2 diabetes and cardiovascular disease (8, 41). Recently, it has been demonstrated that even a 2-wk reduction in daily activity level can be sufficient to increase insulin resistance in healthy subjects, as does 9 days of strict bed rest (1, 26). On the other end of the spectrum, a single bout of exercise can reduce insulin resistance (17), regular physical activity reduces the risk of developing diabetes (21, 29), and significant exercise effects have been reported in diabetics (9), making exercise a powerful tool in the prevention and management of type 2 diabetes.Skeletal muscle accounts for the majority of insulin-induced glucose uptake. Binding of insulin to its receptor on the cellular plasma membrane leads, via the activation of intracellular insulin receptor substrates 1 and 2 (IRS1/2), to translocation of the GLUT4 glucose transporter to the plasma membr...

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“…A total of 39 mutations have been reported so far in the SLC25A20 gene which seem to be pan-ethnic (Wang et al 2011;Indiveri et al 2011); (HGMD Professional Release 2013.4 www.biobase-international.com). Functional characterization has been performed in very few of them.…”

Section: Mutational Findingsmentioning

confidence: 99%

Carnitine-Acylcarnitine Translocase Deficiency: Experience with Four Cases in Spain and Review of the Literature

Vitoria¹,

Martín‐Hernández

Quintana

et al. 2014

JIMD Reports

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Background: Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease in the mitochondrial transport of long-chain fatty acids. Despite early diagnosis and treatment, the disease still has a high mortality rate.Methods: Clinical symptoms, long-term follow-up, and biochemical and molecular results of four cases are described and compared with the reviewed literature data of 55 cases.Results: Two cases with neonatal onset, carrying in homozygosity the novel variant sequences p.Gly20Asp (c.59G>A) and p.Arg179Gly (c.536A>G), died during an intercurrent infectious process in the first year of life despite adequate dietetic treatment (frequent feeding, highcarbohydrate/low-fat diet, MCT, carnitine). The other two cases, one with infantile onset and the other diagnosed in the newborn period after a previous affected sibling, show excellent development at 4 and 16 years of age under treatment. The review shows that the most frequent presenting symptoms of CACT deficiency are hypoketotic hypoglycemia, hyperammonemia, hepatomegaly, cardiomyopathy and/or arrhythmia, and respiratory distress. The onset of symptoms is predominantly neonatal in 82% and infantile in 18%. The mortality rate is high (65%), most in the first year of life due to myocardiopathy or sudden death. Outcomes seem to correlate better with the absence of cardiac disease and with a higher long-chain fatty acid oxidation rate in cultured fibroblasts than with residual enzyme activity.Conclusion: Diagnosis before the occurrence of clinical symptoms by tandem MS-MS and very early therapeutic intervention together with good dietary compliance could lead to a better prognosis, especially in milder clinical cases.

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The mitochondrial carnitine/acylcarnitine carrier: Function, structure and physiopathology

Cited by 217 publications

References 76 publications

The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids

The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids

Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle

Carnitine-Acylcarnitine Translocase Deficiency: Experience with Four Cases in Spain and Review of the Literature

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