Peroxisom

The peroxisome is a membrane-bound organelle, a type of microbody that is found in the cytoplasm of virtually all eukaryotic cells (Islinger M et al. 2018). Peroxisomes are oxidative organelles. Molecular oxygen often serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to their hydrogen peroxide-generating and scavenging activities. They play a key role in lipid metabolism and in the reduction of reactive oxygen species (Bonekamp NA et al. 2009).

Peroxisomes are small (0.1-1 μm diameter) organelles with a fine, granular matrix surrounded by a single biomembrane and located in the cytoplasm of a cell. Compartmentalization creates an optimized environment to promote various metabolic reactions within the peroxisomes that are necessary for the maintenance of cellular functions and the viability of the organism.

The number, size and protein composition of peroxisomes are variable and depend on the cell type and environmental conditions. The diverse functions of peroxisomes require dynamic interactions and cooperation with many organelles involved in cellular lipid metabolism, such as the endoplasmic reticulum, mitochondria, lipid droplets and lysosomes. Peroxisomes contain at least 50 oxidative enzymes that are involved in various biochemical processes in different cell types. The oxidative enzymes produce H2O2. As H2O2 is harmful to the cell, peroxisomes also contain catalase. The enzyme breaks down hydrogen peroxide by converting it into water or using it to oxidize another organic compound. Some other substances such as uric acid, amino acids and fatty acids are also broken down by these oxidative enzymes.

Peroxisomes are involved in the degradation of very long-chain fatty acids, branched-chain fatty acids, intermediates of bile acid (in the liver), D-amino acids and polyamines. Peroxisomes also play a role in the biosynthesis of plasmalogens: ether phospholipids, which are crucial for the normal function of the mammalian brain and lungs. Peroxisomes contain about 10 % of the total activity of two enzymes (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) in the pentose phosphate pathway (Antonenkov VD 1989) which is important for energy metabolism.

Peroxisomes interact with mitochondria in several metabolic pathways, including β-oxidation of fatty acids and metabolism of reactive oxygen species. Both organelles are in close contact with the endoplasmic reticulum and share several proteins, including organelle cleavage factors. Peroxisomes also interact with the endoplasmic reticulum and cooperate in the synthesis of ether lipids (plasmalogens), which are important for nerve cells (see above). In filamentous fungi, peroxisomes hitchhike on microtubules, a process that involves contact with fast-moving early endosomes. Physical contact between organelles is often mediated by membrane contact sites, where the membranes of two organelles are physically connected to allow the rapid transfer of small molecules, enable communication between organelles, and are critical for the coordination of cellular functions and thus for human health.

Changes in membrane contacts have been observed in various diseases.

Peroxisomal diseases are a class of diseases that typically affect the human nervous system as well as many other organ systems, including the skin (seeRefsum syndrome below). One example is X-linked adrenoleukodystrophy.

PEX genes encode the protein machinery (peroxins) required for the proper assembly of peroxisomes. Peroxisomal membrane proteins are imported via at least two pathways, one of which depends on the interaction between peroxin 19 and peroxin 3, while the other is required for the import of peroxin 3. Both pathways can occur without the import of matrix enzymes (lumen) that possess the peroxisomal target signal PTS1 or PTS2. The elongation of the peroxisome membrane and the final cleavage of the organelle are regulated by Pex11p.

The genes encoding peroxin proteins include: PEX1, PEX2 (PXMP3), PEX3, PEX5, PEX6, PEX7, PEX9, PEX10, PEX11A, PEX11B, PEX11G, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26, PEX28, PEX30 and PEX31 (Effelsberg D et al. 2016).

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