Intracellular (hydrophobic/hydrophilic) structure, and the biogenesis of

Intracellular organelles lipid droplets are essential components of the cell that serve as storage sites for neutral lipid storage and play a vital role in lipid metabolism and energy homeostasis. Impaired functioning of lipid droplets is linked to various diseases (3).

Lipid droplets can be formed de novo or they can derive from existing LDs through the process of fission. De novo biogenesis of LDs in eukaryotic cells takes place in the endoplasmic reticulum (ER), where synthesis of neutral lipids occurs. Based on the model for LD formation that we have today, there are three stages: (1) neutral lipid synthesis, (2) lens formation, and (3) drop formation (3).

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Increased levels of intracellular free fatty acids (FAs) trigger LD biogenesis. To avoid lipotoxicity, excessive FAs are being converted into neutral lipids and then stored in cytosolic LDs. Lipid droplets have a unique amphipathic (hydrophobic/hydrophilic) structure, and the biogenesis of these organelles attract a lot of scientific attention. As it was stated above, LD formation initially occurs within the leaflets of ER phospholipid bilayer and involves synthesis of neutral lipids, their progressive accumulation in the ER and formation of cytosolic droplets. When the volume of accumulated neutral lipid between the ER bilayer reaches certain level and exceeds the solubility limits, lipid droplets are ‘oiled out’ from the ER bilayer (2).

According to the model currently accepted neutral lipid lens then buds out from the ER together with the outer leaflet of the bilayer membrane. It is thought that this process involves structural LD associated proteins like PAT, which mediates budding at specific domains of ER bilayer membrane. Newly formed LDs continue to grow due to the excessive amount of intracellular fatty acids until they reach a final size. Their size varies significantly – from 0.4 to 100 ?m – in different cells of the body. Constantly changing pathophysiological conditions result in LDs being of different size within the same cell (1).

Numerous enzymatic reactions are involved into the LD biogenesis, in the process of which many bioactive lipid intermediates are synthesized. LD formation is conducted by apparently superfluous activities of various enzymes and proteins. For instance, it is known today that major long-chain fatty acids can be activated by at least eleven mammalian acyl-CoA synthetases (ACSs) that can also initiate the synthesis of neutral lipids. In humans, at least twelve genes of three different acyltransferase families generate enzymes that are able to catalyze the last step of neutral lipid synthesis. This complexity and functional compensation indicates the physiological significance of the LD, and also how particular proteins and lipids participating in the LD assembly and metabolism are (3).

Amount of lipids stored within the cell varies over time, reflecting the balance between consumption and arrival of lipid droplets. Excess amount of lipids stored in the cell results in the development of fat-related disorders like atherosclerosis or obesity. Accumulation of lipid droplets is extremely heterogeneous even between otherwise identical cells. Factors like intracellular and extracellular stresses activate LD formation, which indicates that LDs actively participate in processes not directly related to lipid metabolism, for example protein degradation or immunity. Experiments confirm that LD accumulation takes place during progression of pathologies that are not related to lipids, such as viral hepatitis, cardiomyopathies, and neuropathies (2).


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