Biology
4. Membrane organelles
Doc. RNDr. Jan Hošek, Ph.D.
hosekj@pharm.muni.cz
Department of Molecular Pharmacy
FaF MU
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Organisation of eukaryotic cell
o Each cell is complex hirearchicaly
organised system
o Main building blocks are proteins,
nucleic acids, polysaccharides, and
lipids
o Cellular organelles are formed by spatial
organisation of main building blocks
o Organelles themselves have multilevel
organisation
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Cellular structures
o Membrane structures
o Fibrilar structures
o Genophores
o Cytoplasm
o Ribosomes
o Cellular inclusions
https://www.osmosis.org/answers/eukaryotic-cell
Differences between eukaryotics and
prokaryotics – quick reminding
PROKYRYOTICS EUKARYOTICS
Cell
organisation
simple complex
Nucleus
any nucleus (only
nukleoid)
full-bodied nucleus
Chromosome one circular one or more linear
Genes w/o intrones
intrones and
exones
Organelles
Only non-
membranes
membranes and
non-membranes
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https://www.sciencefacts.net/prokaryotes-vs-eukaryotes.html
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Plant cell Animal cell
https://science.howstuffworks.com/life/cellular-microscopic/plant-cells-animal-cells.htm
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Compartmentation – theory of endosymbiosis
https://slideplayer.com/slide/10110785/
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Why do cells need organelles?
o Organelles maintain different concentrations of substances in different parts of the
cell. Most important is the maintenance of ion concentration gradients on opposite
sides of the membrane. At the right moment, the cell can then initiate influx or
transport.
o It is advantageous to maintain each
biochemical process in a specific environment
and at certain concentrations. It would be
possible without them, energy and metabolic
transformations would not be as efficient or
would be slow or some could not take place
biochemically at all. The waste products
would also unnecessarily interact with DNA
and other useful molecules inside the cell. pH in cell
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Cell as a city or a fabric
https://www.biologyexams4u.com/2022/12/cell-city-analogy-learn-cell-parts.html
https://prezi.com/
hqun2aj4kqa5/cell-
analogy-a-factory/
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Metabolic net of organelles
o Each organelle has its role
o An intensive exchange of
substances and energy takes
place between the organelles
https://www.healthknot.com/cellular_metabolism.html
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Endoplasmic reticulum (ER)
o Assambly line of cells
o Multiple curved membrane
sheet, which forms closed sac
- endoplasmic lumen
(cisternal space)
o Connected with nucleoplasm
o Membrane of ER represent
more than 50 % of total cell
membranes
o ER lumen occupates up to
10% of cell volume
https://micro.magnet.fsu.edu/cells/endoplasmicreticulum/endoplasmicreticulum.html
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https://www.ncbi.nlm.nih.gov/books/NBK56312
6/figure/article-28660.image.f1/
https://www.histology.leeds.ac.uk/cell/cell_organelles.php
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ER functions
o central role in the synthesis of lipids, proteins, steroids
o biosynthesis and metabolism of own substances and xenobiotics
o it facilitates the formation of the correct tertiary or quaternary structure of proteins
o transport system – distribution of proteins to the cytoplasm or organelles
o maintaining of osmotic pressure
o storage and deposition of Ca2+ ions
o chemical modification of proteins
• disulfide bridges are formed by oxidation of cysteine ​​pairs of side chains
o formation of glycoproteins by covalent attachment of a short oligosaccharide side
chain – is finished in GA
o the oligosaccharide precursor is linked by an O- or N-bonds to a protein molecule
o protein output is controlled = misfolded protein is retained by chaperone or degraded
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Schematic representation of ER functions
Detoxification enzymes
Ca2+
Ca2+
cholesterol
steroid
hormones
toxin - lipid
toxin - water
COO-
COO-
NH2
NH2
transmembrane
protein
misfolded
enzymes of
steroid synthesis
Components of
lipids synthesis
orientation
lumen ER
ER membrane
soluble protein
Glykosylation
S-S bridges
chaperones
SRP Sec61 translocator, SRP receptor
growing bodies
transport to GA
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DOI: 10.1016/j.biocel.2011.10.012
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ER – protein synthesis
o Extracellular proteins and membrane-bound proteins are
formed in ER
o Proteosynthesis starts in cytoplasm
o Proteins are formed by ribosomes on rough ER
o Post-translation modifications in ER – formation of disulfidic
bridges and starting of glycosylationní (continuing in GA)
https://www.zoology.ubc.ca/~berger/B200sample/unit_8_protein_processing/er_targeting/lect27.htm
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ER – lipid synthesis
o Lipids are formed in smooth ER in cooperation with other organelles
o In the ER, storage lipid droplets are also created by a special process by
dislodging and throttling a segment of the ER membrane into the cytoplasm
https://www.intechopen.com/online-first/82195
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ER – detoxification of metabolites and xenobiotics
o Mainly in smooth ER of hepatocytes
o (Probably) the most important is group of P450 cytochromes
• P450 oxidoreductases are very important enzymes for pharmacology
• we know several subtypes - subtypes 3A4 and 2C9 metabolize most of drugs and a number of toxins
and xenobiotics (e.g. into more polar molecules for easier elimination from the body)
o P450 is also involved in the metabolism and synthesis of a number of
important substances, e.g. vitamins, cholesterol, bile acids, steroid
hormones,...
https://doi.org/10.1124/dmd.112.048991
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ER → Sarcoplasmic reticulum (SR)
o Sarcoplasmic reticulum = ER in muscle cells
o SR releases Ca2+ ionts and start muscle contraction
https://www.austincc.edu/apreview/PhysText/Muscle.html
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https://www.austincc.edu/apre
view/PhysText/Muscle.html
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Golgi apparatus (GA) – I.
o Complex of cisternae and vesicles
o Located close to nukleus and ER
o Vesicles – sacs containing proteins
produced in the rough ER deliver their
contents to the cis face of the GA with
which they fuse
o Secretory vesicles – vesicles containing
processed proteins and suffocating from
the trans face of the GA from where they
move to the plasma membrane where
they excrete their contents into the
extracellular environment
https://www.sciencefacts.net/golgi-apparatus.html
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Golgi apparatus (GA) – II.
o Cisternae are connected to each
other and on the side facing the
nucleus (cis face), they
constantly receive vesicles split
off from the ER and intensively
split vesicles filled with various
cell secretions (trans face)
By OpenStax - https://cnx.org/contents/FPtK1zmh@8.25:fEI3C8Ot@10Version
8.25 from the TextbookOpenStax Anatomy and PhysiologyPublished May 18,
2016, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=64286585
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GA functions
o Transport and storage of differnt
compounds
o Posttranslation modification of proteins
• The most common are glycosylation,
phosphorylation, sulphatation, specific proteolysis
o Synthesis of polysaccharides and
immunoglobulins
o Creation of secretory vesicles used during
exocytosis
o Production of materiál for cell wall
o Creation and diferentiation of lysosomes
o Reparation of cell surface
o Creation of vacuols
© 2009 Nature Publishing Group Xu, D. & Esko, J. D. A Golgi-on-achip
for glycan synthesis. Nature Chemical Biology 5, 612–613 (2009)
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https://doi.org/10.1016/B978-0-444-63772-7.00017-8
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Exosomes, endosomes and lysosomes
o Organelles/vesicles with
recycling function
o Exosomes – transport
material outside the cell
o Endosomes - transport
material into cell
o Lysosomes – organelles
digesting phagocytated
material
https://doi.org/10.3390/ijms24021337
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DOI: 10.3389/fimmu.2014.00518
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Exosomes – cellular dustmen
o Vesicles that help remove the waste products of cellular metabolism
o They are formed by the fusion of the cell membrane and the internal parts
of the cell
o Exosomes are part of intracellular communication
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New functions of exosomes
o They can transport proteins, nucleic acids,
lipids and metabolites between cells
o antigen presenting cells share pathogens
that are captured in exosomes =
amplification of immune response
o some exosomes, for example, display Fas
ligand on their surface, which, after binding
to the Fas receptor (also known as the
"death receptor"), initiates apoptosis
o mRNA carried by the exosome can be
translated into a polypeptide in the target
cell
Biogenesis and secretion of exosomes. The secretion of exosomes
involves two invaginations of the plasma membrane. Intercellular
communication mediated by circulating exosomes occurs through
endocytosis, ligand–receptor interaction, and membrane fusion.
Components such as proteins, nucleic acids, lipids, and metabolites are
delivered by exosomes from the source to target cells [33]. Proteins located
in the plasma membrane, including CD63, CD9, CD81, TSG101, and Alix,
are commonly used as markers for exosomes [26].
https://www.mdpi.com/2073-4409/12/2/311
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Exosomes as drug carriers
for tumor immunotherapy
o Extracellular exosomes and
microparticles of immune cells
can influence tumor progression
https://doi.org/10.1016/j.jconrel.2020.09.028
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Recycling of membrane proteins
o Plasma membrane phospholipids
and membrane proteins can be
recycled
o In the endosome, phospholipids
are modified, which serve as
markers for recycling/degradation PI3P
PI3,5P
PI4P
PI3P
https://doi.org/10.1038/nature16868
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Peroxisomes
o Simple organelles capable of "dividing" themselves
o Proteins enter the peroxisomes from the cytoplasm,
where they are formed by free ribosomes
o Functions:
• Oxidation of various substrates → inactivation of toxins, beta-oxidation of
fatty acids
• Detoxification of oxygen radicals (hydrogen peroxide, superoxides and
epoxides) → catalase
• The first steps in the synthesis of glycerolipids or plasmalogens
• Formation of bile acids, dolichol, and cholesterol
https://www.ncbi.nlm.nih.gov/books/NBK9930/