Peroxysome

Peroxisome was first described by Rhodin in 1954 and named

microorganism.
• Although it was previously considered a “fossil organelle” of cells, it
was defined by de-Duve and Baudhuin in 1966 as an organelle
containing catalase, the enzyme that breaks down hydrogen peroxide
(H2O2) into water and oxygen in a protein-dense matrix surrounded
by a single membrane.

• It was renamed peroxisome due to its high amount of peroxidase

activity.
• The single membrane surrounding the peroxisome matrix is ​
characterized by its relatively small width (approximately 7nm) and
low protein/lipid ratio.

• Peroxisomes can adapt to different conditions by changing their size,

morphology, number and enzyme content depending on external
stimuli, the metabolic activity of the cell, the stress it is exposed to or
the stage of development.
Dynamic nature
 Functions of Peroxisome
• The oxidation of fatty acids and the breakdown of H2O2 into water
and oxygen by the enzyme catalase is a common function performed
by all peroxisomes, regardless of the type of organism.

• It is also involved in catabolic and anabolic processes that are

necessary for development and cell survival.
• In human cells peroxisomes are involved in the catabolic role of lipid
metabolism, including β-oxidation of very long chain fatty acids
(VLCFA), alpha oxidation of 3-methyl branched-chain fatty acids, ether
lipids, and bile acid synthesis. and is responsible for its anabolic
functions
• The early steps of the isoprenoid/cholesterol
biosynthetic pathway, which results in
cholesterol synthesis in the endoplasmic
reticulum, also occur in the peroxisome.
• Cholesterol is an essential lipid that
constitutes 30-40% of the total lipid storage in
the cell; In addition to its functions in bile acid
synthesis occurring in the peroxisome, it is
involved in many cellular functions, including
signal transduction, steroid synthesis, and
providing mechanical stability in the cell
membrane.
• Peroxisomes are also involved in the transport
of free cholesterol.
 Biogenesis of peroxysome
1) Fission of pre-existing peroxisomes
(autonomous division) PEX: Perox
• The mechanism is the growth
and division of pre-existing
peroxisomes.
• includes a series of
morphological changes, including
peroxisome proliferation, Dynamin-like GTPase (DRP1), activated by PEX11β, binds to
membrane proteins called mitochondria fission 1 protein (Fis1)
membrane elongation (growth), and mitochondria fission factor (Mff) in the fission of
knurling and, in the final stage, peroxisomes, as in mitochondria, and forms ring-like structures
membrane scission. in the junction regions. The DRP1 ring, which narrows with
GTP hydrolysis, causes the peroxisome membrane to break
and break
Biogenesis of peroxysome

De-Novo Biogenesis The first evidence

Mitochondria

• The newly formed peroxisome • Demonstration of ; peroxisome

occurs by the fusion of two membrane proteins (PMP) can
peroxisome precursor vesicles, be transported from the
one coming from the endoplasmic reticulum via PEX
Endoplasmic reticulum

endoplasmic reticulum, which is proteins.

a source of lipid and protein,
Maturation
Peorxysome

and the other coming from the

mitochondria. Other PMP

In this way, a newly formed peroxisome can

divide into 2-5 daughter peroxisomes.
mt and Perox
• Recent data have shown that in addition to the fission mechanisms of
(being carried out by the same proteins) , they also play a joint role in
innate immunity and indicate that they may be
active in common signaling pathways.
 Protein Transport to Peroxysome
• Peroxisomal targetting sequence (PTS)
1. PTS1 ; located at the carboxyl end of some proteins
2. PTS2 ; located at the amino end of some proteins
3. Peroxisomal membrane targeting sequences (PMTS) are involved in
targeting peroxisome membrane proteins.
Any PQC sysytem at the matrix of
peroxysome has not been defined yet!
• The most important feature that distinguishes peroxisome matrix
proteins from other post-translational transport systems is that they
are folded in the cytosol before targeting, added to cofactors, and
transported to the target after combining into oligomers.
PEX Proteins
Peroxysomal Protein and Organel Quality
Control
• Cytoplasmic PQC; Peroxisome proteins encoded by the nuclear
genome are directed to the peroxisome via the post-translational
transport mechanism. In the peroxisome matrix, which has highly
oxidizing properties, peroxisome proteins fold in the cytoplasm and
combine with their cofactors before transport to reduce the
possibility of peptide misfolding.
• Since there are no effective systems to correct misfolding of
peroxisome matrix proteins in the matrix, peroxisome proteins are
transported after folding.
1st step of peroxisome protein qualitycontrol.
Why perox proteins are prone to miss folding
or unfolding?
• Enzymes that detoxify H2O2, which is formed as a result of chemical
reactions in peroxisomes, prevent the damage that H2O2 may cause
to cellular components.
• Despite all these precautions, peroxisome proteins are prone to
damage due to Why this ofisthe
the nature somatrix
important
in which they are located.
• No peroxisome-specific chaperones have yet been identified.
• 2nd level of PQC; Peroxisomal LonP2, which has both chaperone
and protease activity, destroys damaged proteins in the peroxisome
matrix.
• The functionality of the peroxisome is preserved by ensuring matrix
protein homeostasis and preventing the accumulation of oxidative
damage.
3) Peroxisome quality control is 15-LOX-
mediated autolysis
• 15-LOX, a member of the lipoxygenase (LOX) family, converts
polyunsaturated fatty acids into conjugated hydroperoxides, causing
the membrane structure of the organelle to deteriorate.

• This process ends with the peroxisome content diffusing into the
cytoplasm and destroying the cell by autolysis.
• Pexophagy is a type of selective autophagy and constitutes an
important step of organelle quality control by destroying damaged
and/or unnecessary peroxisomes in the lysosome.

starvation

Hearing loss
Ub dependent UB independent