0000000000241469
AUTHOR
Françoise Le Borgne
Characteristics of l-carnitine import into heart cells
Abstract l -carnitine is an essential cofactor for the transport of fatty acids across the mitochondrial membranes. l -carnitine can be provided by food products or biosynthesized in the liver. After intestinal absorption or hepatic biosynthesis, l -carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as the skeletal muscle and the heart. The intracellular transport of l -carnitine into the cell requires specific transporters and today, several of these have been characterized. Most of them belong to the solute carrier family. Heart is one of the major target for carnitine transport and use, however basic properties of carnitine uptake by heart ce…
Hormonal and nutritional control of L‐carnitine uptake in myoblastic C2C12 cells
L-Carnitine plays an important role in skeletal muscle bioenergetics, and its bioavailability and thus its import may be crucial for muscle function. We studied the effect of thyroid hormone, insulin, and iron overload, hormones and nutrients known to alter muscle metabolism, on L-carnitine import into C2C12 cells. We report here L-carnitine uptake is increased by thyroid hormones and decreased by iron. Insulin was found to be ineffective in altering the L-carnitine uptake.
Changes in carnitine octanoyltransferase activity induce alteration in fatty acid metabolism
The peroxisomal beta oxidation of very long chain fatty acids (VLCFA) leads to the formation of medium chain acyl-CoAs such as octanoyl-CoA. Today, it seems clear that the exit of shortened fatty acids produced by the peroxisomal beta oxidation requires their conversion into acyl-carnitine and the presence of the carnitine octanoyltransferase (CROT). Here, we describe the consequences of an overexpression and a knock down of the CROT gene in terms of mitochondrial and peroxisomal fatty acids metabolism in a model of hepatic cells. Our experiments showed that an increase in CROT activity induced a decrease in MCFA and VLCFA levels in the cell. These changes are accompanied by an increase in …
Extracellular ATP Increases <i>L</i>-Carnitine Transport and Content in C2C12 Cells
Extracellular ATP regulates cell proliferation, muscle contraction and myoblast differentiation. ATP present in the muscle interstitium can be released from contracting skeletal muscle cells. <i>L</i>-Carnitine is a key element in muscle cell metabolism, as it serves as a carrier for fatty acid through mitochondrial membranes, controlling oxidation and energy production. Treatment of C2C12 cells with 1 mmol/l of ATP induced a marked increase in <i>L</i>-carnitine uptake that was associated with an increase in <i>L</i>-carnitine content in these cells. These effects were found to be dependent on the density of the cultured cells and on the dose of ATP. The…
Crosstalk between mitochondria and peroxisomes
Mitochondria and peroxisomes are small ubiquitous organelles. They both play major roles in cell metabolism, especially in terms of fatty acid metabolism, reactive oxygen species (ROS) production, and ROS scavenging, and it is now clear that they metabolically interact with each other. These two organelles share some properties, such as great plasticity and high potency to adapt their form and number according to cell requirements. Their functions are connected, and any alteration in the function of mitochondria may induce changes in peroxisomal physiology. The objective of this paper was to highlight the interconnection and the crosstalk existing between mitochondria and peroxisomes. Speci…
Exploration of lipid metabolism in relation with plasma membrane properties of Duchenne muscular dystrophy cells: influence of L-carnitine.
Duchenne muscular dystrophy (DMD) arises as a consequence of mutations in the dystrophin gene. Dystrophin is a membrane-spanning protein that connects the cytoskeleton and the basal lamina. The most distinctive features of DMD are a progressive muscular dystrophy, a myofiber degeneration with fibrosis and metabolic alterations such as fatty infiltration, however, little is known on lipid metabolism changes arising in Duchenne patient cells. Our goal was to identify metabolic changes occurring in Duchenne patient cells especially in terms of L-carnitine homeostasis, fatty acid metabolism both at the mitochondrial and peroxisomal level and the consequences on the membrane structure and functi…
A high-fat diet increases l-carnitine synthesis through a differential maturation of the Bbox1 mRNAs.
International audience; l-carnitine is a key molecule in both mitochondrial and peroxisomal lipid metabolisms. l-carnitine is biosynthesized from gamma-butyrobetaine by a reaction catalyzed by the gamma-butyrobetaine hydroxylase (Bbox1). The aim of this work was to identify molecular mechanisms involved in the regulation of l-carnitine biosynthesis and availability. Using 3' RACE, we identified four alternatively polyadenylated Bbox1 mRNAs in rat liver. We utilized a combination of in vitro experiments using hybrid constructs containing the Bbox1 3' UTR and in vivo experiments on rat liver mRNAs to reveal specificities in the different Bbox1 mRNA isoforms, especially in terms of polyadenyla…
Carnitine transport into muscular cells. inhibition of transport and cell growth by mildronate
Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is found in dairy and meat products, but is also biosynthesized from lysine and methionine via a process that, in rat, takes place essentially in the liver. After intestinal absorption or hepatic biosynthesis, carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle. In skeletal muscle, carnitine concentration was found to be 50 times higher than in the plasma, implicating an active transport system for carnitine. In this study, we characterized this transport in isolated rat myotubes, established mouse C2C12 myoblastic cells, and …
L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death.
International audience; AIMTo identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells.METHODSMyoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine (a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death.RESULTSAssociated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species (ROS), especially under pathological conditions. High levels o…
Beneficial effects of l-carnitine in myoblastic C2C12 cells
L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side e…
L-Carnitine Supplementation and Physical Exercise Restore Age-Associated Decline in Some Mitochondrial Functions in the Rat
In mammals, during the aging process, an atrophy of the muscle fibers, an increase in body fat mass, and a decrease in skeletal muscle oxidative capacities occur. Compounds and activities that interact with lipid oxidative metabolism may be useful in limiting damages that occur in aging muscle. In this study, we evaluated the effect of L-carnitine and physical exercise on several parameters related to muscle physiology. We described that supplementing old rats with L-carnitine at 30 mg/kg body weight for 12 weeks (a) allowed the restoration of L-carnitine level in muscle cells, (b) restored muscle oxidative activity in the soleus, and (c) induced positive changes in body composition: a decr…
Radioisotopic determination of l-carnitine content in foods commonly eaten in Western countries
Abstract l -Carnitine is a vitamin-like nutrient essential for energy production and lipid metabolism in many organs and tissues such as skeletal muscle and heart. Even if l -carnitine can be synthesized, most of the carnitine present in human body is provided by food. Until now, no large study has been conducted where the content in l -carnitine of various foods was analyzed. The objective of this study was to determine the level of free l -carnitine present in food commonly consumed in Western countries. A radioisotopic assay was used to estimate l -carnitine content in raw and processed foods. From this study, it clearly appeared that meat products were the best sources for l -carnitine.…
Interaction between peroxisomes and mitochondria in fatty acid metabolism
Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for most (mitochondria) or all (peroxisome) of them, synthesized in the cytosol from the nuclear genome. Nevertheless, the membrane structures and the DNA content differ between these two organelles. Mitochondria possess a small circular genome while peroxisomes don’t. The control of their dynamic is dependent on specific factors even if some of those are able to affect both. These two organelles are metabolically connected: they are both involved in lipid metabolism. They are both a…