Cell nucleus,

mitochondrium,
peroxysome

Viktoria Vereczki, M.D., Ph.D.

Cell nucleus

- cell nucleus
- cytoskeleton
- RNA synthesis (transcription) and protein
synthesis (translation) are separated
 The cell nucleus

The cell nucleus is surrounded by the nuclear envelope (also called nuclear
membrane, nucleolemma, or karyotheca).

The material within the nuclear envelope is the nucleoplasm or karyoplasm.

The components of the karyoplasm:

• DNA and its associated proteins, the chromatin
• skeletal elements, the nucleo- or karyoskeleton
• the fluid material surrounding the karyoskeleton and the chromatin, the nucleo-
or karyosol

Chromatid: one DNA chain and its associated proteins

Chromosome: densely packed ´transport´ form of chromatin with characteristic
shape during cell division. In functional sense, the term is also used for the
intermitotic phase.
The nuclear envelope: a double lipid bilayer that
encloses the genetic material in eukaryotic cells

The outer membrane is

continuous with the
endoplasmic reticulum
 Nuclear lamina (the major component of nucleoskeleton) is
attached to the inside surface of the inner nuclear membrane
Electron microscopic image of the nuclear
lamina: a 2D mesh
 The function of nuclear lamina: to stabilize
nuclear envelope and to bind chromatin

The nuclear lamina consists of 3 types of lamin proteins: A, B, and C.

Lamin A and C bind chromatin, whereas lamin B binds them to the nuclear
membrane via lamin B receptor, an integral membrane protein.
Phosphorylation of lamins leads to the disassembly of the structure during cell
division.
A mutation of lamin A causes Hutchinson-Gilford progeria, an early aging
syndrome.
 The structure of the nucleoplasma

HC - Heterochromatin (electron dense granules): densely packed DNA without transcription

It has 2 forms, the constitutive HC, which is never transcribed, and is usually attached to
the nuclear envelope via the nuclear lamina. In contrast, facultative heterochromatin is
densely packed only in a particular cell type but could also be euchromatin.
EC - Euchromatin: less coiled DNA, the functional part of chromatin with intense mRNA synthesis
NU - Nucleolus: contains genes for ribosomal RNA
 Nucleus

Euchromatine

Heterochromatine

Nucleolus

Heterochromatine

Euchromatine
Pattern of the nucleuplasma: heterochromatic - euchromatic

euchromatic: transcriptionally active  less condensed

often (but not always)is under active transcription
fibroblast neuron

heterochromatic: transcriptionally inactive  highly condensed

is a tightly packed form of DNA there is not RNA synthesis there (fibrocytes)
Special pattern in plasma cells
„clockwise appearance”
 The chromosomes have a territoreal
arrangement within the nucleus

Figure 5-18 Essential Cell Biology (© Garland Science 2010)

The structure of the nucleolus

NE - nuclear envelope
NO - nucleolar organizer, parts of
---------- the chromosomes that
organize ------ nucleolus after
division
A - pars amorpha: DNA encoding
-------rRNA
PF - pars fibrosa, primary rRNA
-----------transcripts
PG - pars granule, maturing
----------------ribosomal subunits
NAC - nucleolus-associated
------------------chromatin
The compact structure of chromosomes during mitosis
 The 23 chromosome pairs of the human genom
Karyotype: chromosomes articially lined
FISH: fluorescent in situ hybridization
up in order (e.g. for cytogenetic analysis)
The basic organizational unit of DNA in
chromosomes: the nucleosome
 A linker histon (H1) determines the angle how linker DNA leaves
the core of the nucleosomes allowing further condensation

Figure 5-24 Essential Cell Biology (© Garland Science 2010)

 Aberrant chromosomes are associated with
genetic deficits

An abnormally longer
chromosome 12 from a
patient with inherited
ataxia

Figure 5-12 Essential Cell Biology (© Garland Science 2010)

Different levels of DNA packing

The 30 nm solenoid structure fiber

forms loops whose base is attached
to scaffold proteins.
Decondensation of these loops
allows the transcription of genes
they encode.
 Chromatin-remodeling complexes decondense the
chromatin making it accessible to other proteins for
replication, transcription and their regulations

Figure 5-27b Essential Cell Biology (© Garland Science 2010)

   nucleus: heterochromatin, euchromatin, and nucleolus
Euchromatin is a lightly packed form of chromatin (DNA, RNA and protein)
that is rich in gene                                      
concentration, and is often (but not always)is under active transcription,

Heterochromatin is a tightly packed form of DNA there is not RNA synthesis there
Histones play a role in the regulation of gene expression
by their posttranslational modifications

Potential posttranslational modifications on the N-terminal tail of Histone 3:

M – methylation
A – acetylation by histone-modifying enzymes
P – phosphorylation

Figure 5-28a Essential Cell Biology (© Garland Science 2010)

 The structure of chromatin varies along a single
interphase chromosome

Figure 5-31 Essential Cell Biology (© Garland Science 2010)

 Histone modifications (and thus gene silencing)
may be inherited by daughter chromosomes – a
mechanism of epigenetic inheritance

Figure 5-32 Essential Cell Biology (© Garland Science 2010)

Nuclear membrane
- is a double lipid bilayer that encloses the genetic material in eukaryotic cells.

- The nuclear membrane also serves as the physical barrier, separating the contents

of the nucleus (DNA in particular) from the cytoplasm.

- Many nuclear pores are inserted in the nuclear membrane, which facilitate and regulate

the exchange of materials (proteins such as transcription factors, and RNA) between the

nucleus and the cytoplasm.

Nuclear pores in the nuclear envelope shown by cryofracture EM
  
nuclear membrane and nuclear poles, neurofilaments
                                      
The nuclear pore complex

The nuclear pore is made

of about 30-100
nucleoporin proteins.
The mechanism of gating by the nuclear pore complex

Proteins that assist the nuclear

transport are called nuclear
transport receptors, NLS
receptors, or karyopherins
(importins into the nucleus and
exportins out of the nucleus).

First the NLS receptor (importin

alpha) recognizes the protein.
They reach the FG (Phe-Gly)
repeats of pore fibrils by which
they approach the central pore.
Importin beta binds to
nucleoporins within the central
pore and allows the passage of
the recognized proteins.
After crossing the pore, the
importins are removed from the
protein.
 Mitochondrion
established them as cell organelles
Richard Altmann (1886) german pathologist

mitos= "thread”  chondrion= "granule"

”Powerhouse of the cell”

Philip Siekevitz (1957) american biochemist
 Ultrastructure of the Mitochondria

matrix

inner membrane

outer membrane

intermembrane space
cristae
 Membranes of the Mitochondria

Outer membrane: smooth, special proteins (porins), translocon complexes (TOM, TOB)
and phospholipids. Permeable to nutrient molecules, ions, ATP and ADP
Inner membrane: folded (cristae-increased surface), kardiolipin (regulation of membrane
permeability of ions) complexes for electron transport, ATP synthase complexes, transfer
regulating proteins (TIMs). Permeable for oxigene, carbon dioxide, water
 Nobel prize winners

Albert Szentgyörgyi Hans Adolf Krebs Peter Daniel Mitchell

1893-1986 1900-1981 1920-1992

Nobel prize in Physiology Nobel prize in Physiology Nobel prize in Chemistry

and Medicine (1937) and Medicine (1953) (1978)
Vitamin C and catalysis of Citric Acid Cycle Chemiosmotic theory
fumaric acid, Szentgyörgyi- Szentgyörgyi-Krebs Cycle
Krebs Cycle
Chemiosmotic theory by Nobel prize winner Peter Mitchell (1978)
 Major function of the Mitochondria:
-Outer membrane:
-Transport functions, most substances are also transported through the inner membrane.

-Inner membrane (other translocons):

-Proton-transport and oxydative phosphorylation
- Ca”+ transport (to sequester the the Ca2+ from the cytoplasm)
- Lipid, aminoacid, ADP, phosphate, pyruvate transport inward, ATP outward
- Transports of proteins (mitochondrial enzymes), tRNA (through translocons).

-Matrix:
- Citrate cycle (Krebs- or Szentgyörgyi-Krebs-cycle);
- Lipid- and aminoacid-degradation to acetyl-groups for the citrate cycle;
- Protein- and lipid synthesis (their special lipid is the cardiolipin).
- Ca”+ storage.
Beside these, mitochondria can grow, divide, move (along microtubules), and if their content is released into the cytoplasm, it switches the apoptotic cascade in

Other functions: heat production, involvement in steroid synthesis and apoptosis

 Mitochondrial matrix
Enzymes
Special mitochondrial
ribosomes
tRNAs
DNA
Carbon dioxide and
oxygen

mtDNA

37 genes → 13 genes enzymes for oxidative

phosphorilation, others for tRNA and rRNA
The majority of proteins in mitochondria are coded by
nuclear DNA
Mitochondrial division

No de novo formation of
mitochondria
1. Replication of genom
2. Growth
3. Fission
4. Segregation
Mitochondria are maternally inherited
fertilization

sperm
 Intracellular location of mitochonrion
In most cells disordered, often along microtubules
In some cells: where a lot of ATP is required

Kidney tubule Heart muscle Spermatide

 Mitochondreal diseases

Kearns–Sayre syndrome (mitochondrial myopathy)

pigmentary retinopathy
cardiac conduction abnormalities
weakness of facial, pharyngeal, trunk and extremity muscles 

Leigh syndrome (mtDNA mutation)

failure to thrive
progressive loss of mental and movement abilities 
„three parent baby”

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis,

and stroke)
 Peroxysome
"Microbody"
small (d= 0.1 - 1 μm)
Outer lipid bilayer, inside finely granulated substance
in some mammals (e.g., rat), the core crystallized in the
middle
(consisting of urate oxidase)

Contains 2 enzymes: peroxidase and katalase

Occurrence: all cells, but especially in those where

detoxification
(liver cells, renal tubules) or intensive lipid metabolism
(myelin sheath,
sebaceous gland) is running.

Origin: either from ER or by division from an existing

peroxysome
Proteins are produced in the cytosol on free ribosomes
and
be with the help of peroxins (different proteins) are
transported the cell organelle.
 Function
Lipid synthesis and oxidation
Detoxification (liver, kidney): phenol, ethanol,
formaldehyde
Protection against oxygen radicals

Enzymes
Peroxidase: withdraw H from molecules using
O2 R - H2 + O2 H2O2

Katalase: 2 H2O2  2 H2 O + O 2

Other enzymes:
Peroxisomal diseases

Zellweger-Syndrom
poor muscle tone (hypotonia)
poor feeding
seizures
hearing loss
vision loss
distinctive facial features
skeletal abnormalities

Neonatal adrenoleukodystrophy
 hypotonia
leukodystrophy
vision and sensorineural hearing deficiencies
Nuclear membrane: nm – membrane, np - pores, nu - nucleoli, m – mitochondrium,
double arrow – transition between nm and endoplasmic reticulum
1 – peroxisome (microbody), 2 – crystalloid (crystalized carbamide oxydase enzyme),
3 – glycogene granules, 4 – mitochondria, 5 – rER
Literature

Alberts: Molecular biology of the cell (Third edition, 1994)

Kovács: Sejttan (1999)

Dr. Baksa: Miochondrium, peroxysom

Dr. Kántor: Miochondrium, peroxysom
Dr. Kántor: Zellkern, Zytoskeleton
Dr. Zachar, Zsíros: Mitokondrium, peroxiszóma
Dr. Pálfi Cell nucelus, mitochondrion, peroxysomes

https://en.wikipedia.org/wiki/Prokaryote#/media/File:Celltypes.svg
https://biologydictionary.net/cell-nucleus/
https://www.biologyexams4u.com/2012/06/nucleus-ultra-structure.html
https://en.wikipedia.org/wiki/Kearns%E2%80%93Sayre_syndrome
https://ghr.nlm.nih.gov/condition/leigh-syndrome#genes
https://emedicine.medscape.com/article/946864-overview
https://rarediseases.info.nih.gov
https://bocaprepetc.weebly.com/atp-synthase.html