15.20: Protein Import into the Peroxisomes
Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome by a group of proteins called peroxins. Peroxisomal receptors recognize the cytosolic proteins by short import sequences at their C- or N-terminus as PTS1 and PTS2, respectively. Proteins from the ER are packaged into specialized vesicles that help transport and insert the protein into the membrane. Unlike other systems such as mitochondria, peroxisomal import machinery can transport fully folded proteins. PEX genes encode for peroxin proteins. Around fifteen PEX genes coding for 32 proteins are known in humans.
Peroxisomal diseases:
The absence or malfunctioning of peroxisomal enzymes in animals results in many metabolic disorders. For example, Zellweger syndrome, an inherited human disease, occurs due to the lack of peroxisomal enzymes or “empty peroxisomes.” Mutations in the Pex5 gene, which encodes peroxin, and defects in the Pex7 gene, which encodes a receptor, cause one form of Zellweger, leading to severe brain, kidney, and liver abnormalities. Adrenoleukodystrophy is a rare X-linked genetic defect that affects the transport and oxidation of long-chain fatty acids in the peroxisomes resulting in the accumulation of fatty acids in the bloodstream. This disease also leads to myelin damage in neurons, affecting the brain's white matter.
