Voortgezette Celbiologie Evelien Floor
Peroxisome biogenesis
Introduction
All eukaryotes have peroxisomes. Peroxisomes are mostly spherical vesicles bounded by a single
membrane. They are abundant, and formation is inducible; if you grow cells in fatty acids they will
produce peroxisomes to degrade it. They were thought to be independent just like mitochondria but
nowadays there is proof that they aren’t. Peroxisomes have a respiration based on H 2O2 producing
oxidases and they use catalase to decompose it. They have -oxidation enzymes for fatty acidoxidation enzymes for fatty acid
degradation. In human they also synthesize myelin (neuron).
There are two types of peroxisomal diseases; peroxisomal biogenesis disorders and peroxisomal
enzyme deficiencies. Zellweger spectrum syndrome is a peroxisome biogenesis disorder. The
disturbed peroxisomal metabolism results in the absence of peroxisomes. People with this disorder
have a high concentration of very long-oxidation enzymes for fatty acidchain fatty acids in blood and die soon after birth. Peroxisomal
enzyme deficiencies (PED) are characterized with much milder clinical phenotypes. Disease
management is a real viable option for instance an altered diet.
There are two theories about the origin of peroxisomes; they are inventions by primitive eukaryotes
or they are domesticated bacterial symbionts. In other words, are they derived or autonomous
organelles?
Autonomous organelles:
Double membrane bound
Contain DNA
Protein import via targeting
signals/import machinery
Inheritance tightly regulated
Derived organelles:
Single membrane bound
Do not contain DNA
Protein import via secretory
vesicles
Stochastic inheritance
The first theory for peroxisome biogenesis was that folded membrane and matrix proteins are
imported via post-oxidation enzymes for fatty acidtranslational import and that they form by growth and division. The experimental
validation of this model was the existence of peroxisomal targeting signals (PTS1, PTS2, mPTS) and a
peroxisomal protein machinery. For this reason, many people thought this model was the right one.
Nowadays we know that peroxisomes have features of both an autonomous and a derived organelle.
The killer experiment:
Take a yeast cell and fluorescently label a protein in the peroxisomes. The PEX3 gene was knocked
out because it is responsible for import of proteins into the peroxisomes. Then, you end up with a
yeast cell without peroxisomes and the protein is distributed over the cell. Afterwards you introduce
PEX3 into the cell. There are two options: if peroxisomes are autonomous there will change nothing
but, in this case, there was complete reformation of the peroxisomes. This was very strong evidence
that peroxisomes are derived from another organelle.
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Peroxisome biogenesis
Introduction
All eukaryotes have peroxisomes. Peroxisomes are mostly spherical vesicles bounded by a single
membrane. They are abundant, and formation is inducible; if you grow cells in fatty acids they will
produce peroxisomes to degrade it. They were thought to be independent just like mitochondria but
nowadays there is proof that they aren’t. Peroxisomes have a respiration based on H 2O2 producing
oxidases and they use catalase to decompose it. They have -oxidation enzymes for fatty acidoxidation enzymes for fatty acid
degradation. In human they also synthesize myelin (neuron).
There are two types of peroxisomal diseases; peroxisomal biogenesis disorders and peroxisomal
enzyme deficiencies. Zellweger spectrum syndrome is a peroxisome biogenesis disorder. The
disturbed peroxisomal metabolism results in the absence of peroxisomes. People with this disorder
have a high concentration of very long-oxidation enzymes for fatty acidchain fatty acids in blood and die soon after birth. Peroxisomal
enzyme deficiencies (PED) are characterized with much milder clinical phenotypes. Disease
management is a real viable option for instance an altered diet.
There are two theories about the origin of peroxisomes; they are inventions by primitive eukaryotes
or they are domesticated bacterial symbionts. In other words, are they derived or autonomous
organelles?
Autonomous organelles:
Double membrane bound
Contain DNA
Protein import via targeting
signals/import machinery
Inheritance tightly regulated
Derived organelles:
Single membrane bound
Do not contain DNA
Protein import via secretory
vesicles
Stochastic inheritance
The first theory for peroxisome biogenesis was that folded membrane and matrix proteins are
imported via post-oxidation enzymes for fatty acidtranslational import and that they form by growth and division. The experimental
validation of this model was the existence of peroxisomal targeting signals (PTS1, PTS2, mPTS) and a
peroxisomal protein machinery. For this reason, many people thought this model was the right one.
Nowadays we know that peroxisomes have features of both an autonomous and a derived organelle.
The killer experiment:
Take a yeast cell and fluorescently label a protein in the peroxisomes. The PEX3 gene was knocked
out because it is responsible for import of proteins into the peroxisomes. Then, you end up with a
yeast cell without peroxisomes and the protein is distributed over the cell. Afterwards you introduce
PEX3 into the cell. There are two options: if peroxisomes are autonomous there will change nothing
but, in this case, there was complete reformation of the peroxisomes. This was very strong evidence
that peroxisomes are derived from another organelle.
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