Nucleus, cell cycle, apoptosis, autophagy, necrosis

Nucles

• contains genome

• can display different shapes

• is not present during the whole cell cycle

• can be missing in some “cells” (blood red cells)

• more than one nucleus can be present in a cell (e.g.syncytium *)

Nucleus structure

• enveloped by a double-bilayer membrane  - delimiting the perinuclear space called nuclear envelope.

• consists of an inner and an outer  membrane separated by a perinuclear cisternal space and perforated by nuclear pores

• The  outer membrane of the nuclear envelope is  continuous with that of the rough-surfaced endoplasmic reticulum (rER) and is

• often studded with ribosomes. 

• Chromatin

• nuclear material organised as euchromatin or heterochromatin contains DNA associated with roughly and equal mass of various nuclear proteins - necessary for DNA to function

Nuclear lamina

• formed by intermediate filaments and lies adjacent to the inner nuclear membrane

  Function

• supports the nucleoskeleton

• Essential in processes like:

  • DNA replication

  • Transcription

  • Gene regulation

• Major component - nuclear lamins - specialised intermediate filament and lamin-associated proteins

Nuclear pores

• 70 to 80 nm openings

• Formed by merging the inner and outer membranes of the nuclear envelope

• Forms nuclear pore complex - close-fitting or gated channel

• Proteins directed to nucleus present specific signal sequences for nuclear import: Nuclear localisation signals (NLS)

Nucleolus

• non membranous region of the nucleus

• Granular appearance

• surround transcriptionally active rRNA genes

• free in nucleoplasm

• Primary site - for ribosome production and assembly

• Varies in size - but particularly well developed in cells in protein synthesis

Cell cycle

• period of time between to cell division

• Can last from hours to days

  • Yeast and bacteria: 2-4 hours 

  • Intestinal, epithelial cells,  erythroblast: 12 hours 

  • Hepatocytes: 1 year 

  • Neurones and muscle tissue never   divide during adult life, howeve,r   they contain stem cells that in case 

• STAGES

  • G0 - Quiescence, resting phase for undefined time. Cell division can be activated via internal stimuli or exogenous growth factors (damages for example). 

  • G1 (8 hours) - Cellular growth, protein synthesis and duplication of organelles. The cell is preparing for division. 

  • S (7-10 hours) - DNA duplication 

  • G2 (2-5 hours) - Microtubules and mitotic spindle appearing, synthesis of cytoplasm components 5. M (1-2 hours) - Mitosis

Prophase

• begins as the replicated chromosomes condense and become visible.

• chromosomes continue to condense, each of the four chromosomes derived from each homologous pair can be seen to consist of two chromatids.

• late prophase - the nuclear envelope begins to disintegrate into small transport vesicles and resembles the sER. The nucleolus, which may still be present in some cells, also completely disappears

• Microtubules of the developing mitotic spindle attach to the chromosomes.

4. Telophase

• marked reconstitution of a nuclear envelope around the chromosomes at each pole. The chromosomes uncoil and become indistinct except at regions that will remain condensed in the interphase nucleus.

• The nucleoli reappear, and the cytoplasm divides (cytokinesis) to form two daughter cells. The separation at the cleavage furrow is achieved by a contractile ring consisting of a  very thin array of actin filaments positioned around the perimeter of the cell.

• Myosin II molecules are assembled into small filaments that interact with the actin filaments, causing the ring to contract. As the ring tightens, the cell is pinched into two daughter cells, genetically identical and containing the same kind and number of chromosomes. The daughter cells are (2d) in DNA content and (2n) in chromosome number. 

3. Anaphase

• begins at the initial separation of sister chromatids.

• occurs when the cohesins that have been holding the chromatids together break down.

• chromatin begin to separate and are pulled to opposite poles of the cell by the molecular motors (dyneins) sliding along the kinetochore microtubules toward the MTOC. 

2. Metaphase

• mitotic spindle, consisting of three types of microtubules, becomes organis around the microtubule-organising centres (MTOCs) located at opposite poles of the cell.

• Microtubule are pulled toward the MTOC, where additional microtubules will attach. Microtubules and their associated motor proteins direct the movement of the chromosomes to a plane in the middle of the cell,  the equatorial or metaphase plate. 

Meisosi

• Carried out by gonads - only cells that propagate genetic information to next generation

• two nuclear divisions - followed by cell divisions that produce gametes

• gamete - contains half the DNA and chromosomes found in Somatic cells

• 2 successive mitotic divisions without the S phase between the divisions

• During the S phase that precedes meiosis, DNA is  replicated forming sister chromatids (two  parallel strands of DNA) joined together by  

  the centromere.

• The DNA content becomes  (4d), but the chromosome number remains the same (2n). The cells then undergo a  reductional division (meiosis I) and an equatorial division (meiosis II).

• Reduce chromosome number from diploid (2n) to haploid (n) 

• Ensure that each daughter cell has one  

• full set of chromosomes 

• Promote genetic diversity 

Cell renewal

Static cell populations

• consist of cells that no longer divide (postmitotic cells), such as cells of the central nervous system and skeletal or cardiac muscle cells.

• Under certain circumstances, some of these cells  (cardiac myocytes) may enter mitotic division. 

Stable cell populations

• consist of cells that divide episodically and slowly to maintain normal tissue or organ structure.

• These cells may be stimulated by injury to become more mitotically active. Periosteal and perichondrial cells, smooth muscle cells, endothelial cells of blood vessels, and fibroblasts of the connective tissue may be included in this category.  

Renewing cell populations

• may be slowly or rapidly renewing but display regular mitotic activity. Division of such cells usually results in two daughter cells that differentiate both morphologically and functionally or  two cells that remain as stem cells.

• Daughter cells may divide one or more times before their mature state is  reached. The differentiated cell may ultimately be lost from the body.

Types of tissue populations

Slowly renewing populations include smooth muscle cells of most hollow organs, fibroblasts of the  uterine wall, and epithelial cells of the lens of the eye. Slowly renewing populations may actually slowly  increase in size during life, as do the smooth muscle cells of the gastrointestinal tract and the epithelial  cells of the lens. 

• Rapidly renewing populations include blood cells, epithelial cells and dermal fibroblasts of the skin, and  the epithelial cells and subepithelial fibroblasts of the mucosal lining of the alimentary tract. 

These are differentiated cells, that differ from stem cells: after a stem cell becomes activated, it replicates  into two daughter cells, one will go back to the rest (maintaining the pool stable) and the one will actually  differentiate.  

Also, the maintenance of the number of cells in a tissue is based on a balance of different processes:  proliferation, differentiation, cell death. 18

Apoptosis

• programed cell death

• Mode of cell that occurs under normal conditions

• Cells undergoing apoptosis show the  

• following characteristic morphologic and biochemical features: 

  • DNA fragmentation - cut within nucleosomes

  • Cytoplasm modification - release of cytochrome C from mitochondria - activation of enzymes able to digest several cytoplasmic and nuclear substrates

  • Destruction of mitochondria physiology - depolarization of mitochondrial membrane potential - alteration of membrane permeability with release of cytochrome C in cytoplasm

  • Decreased cell dimension

  • Modification of plasma membrane - distribution of membrane phospholipids id modified - phosphatidylserine - translates from the cytoplasmic side to extracellular face of plasma membrane

Necrosis

• cell death after injury

• cell swells

• cell lysis - break leading to tissue inflammation

Autophagy

Role

• get ride of aged and damaged organelles and molecules

• autophagy generates fuel and re-utilises components for cellular renewal and repair

• Autophagy - helps in the elimination of pathogens

• Involved in protection against neoplastic transformation and other diseases

Process

1. Creation of phagophore - vesicle formed during initial phase of autophagy - engulf cytoplasmic components

2. Develop into autophagosome - an organelle that encloses parts of cytoplasm into a membrane

3. fuses with lysosome -releasess lysosomal hydrolase - content is degraded