meiosis, organelles and cell death

Question 1

sexual reproduction

Answer 1

• requires specialised cells: gametes
• somatic cells: 44 autosomes and 2 sex ch: diploid: 2n in most cycle and 4n in S and anaphase
• mature germ cells (gametes): 23 single chromosomes: haploid: 1N
• fusion of m and f gametes restores non-germ diploid cell
• requires meiosis to produce haploid cells

Question 2

1st meiotic devision products

Answer 2

• 2 secondary spermatocytes 2N
  or
• 1 secondary oocyte + 1 polar body 2N

Question 3

2nd meiotic division products

Answer 3

• 4 round spermatids 1N
  or
• 1 oocyte and 3 polar bodies 1N
• m and f gametogenesis result in different number of gametes
• primary oocyte produces one mature gamete
• primary spermatocyte produces four spermatids all developing into spermatozoa

Question 4

homologous chromosomes

Answer 4

• same type of info but may be different

Question 5

1st meiotic division

Answer 5

• homologous chromosomes pair (4 chromatids)
• they interchange chromatid fragments in crossing over (not chiasma)
• pull apart in anaphase: hmc segregate

Question 6

2nd meiotic division

Answer 6

• chromatids split at centromere: sisters segregate
• completion: ch in each daughter cells are different

Question 7

crossing over and casual segregation

Answer 7

• enhance genetic variability
• crossing over in prophase 1
• exchanges are random
• separation in anaphases are random

Question 8

primordial germ cells

Answer 8

• PCG, gonocytes
• both type of germ cells derive from PCGs
• undergo a few mitotic divisions after they are invested by the somatic support cells which then differentiate into Sertoli cells

Question 9

gametogenesis

Answer 9

• different time for m and f
  -PCG enter meiosis in the foetal gonad (3-5m)
• differentiate into spermatogonia
• male meiosis inhibitor produced by sertoli cells in male gonad: spermatogonia do not proceed into spermatocytes during this phase: do in puberty under testosterone and proceeds thru adult life
• oogonia are no longer present after 5 month: oocytes present

Question 10

lysosomes

Answer 10

• digesting food and invaders
• recycling cellular components
• cell suicide
• not found in plant cells

Question 11

autophagy

Answer 11

• intracellular degradation system that delivers cytoplasmic constituents to the lysosome
• when cell is deprived
• reuses junk
• physiological and pathophysiological roles
  1. sequestration:formation of phagosome
  2. transport to lysosomes
  3. degradation
  4. utilisation of degradation of products

Question 12

lysosomal storage diseases

Answer 12

• more than 40
• fabry disease
• gaucher disease
• hurler syndrome
• lack of enzymes

Question 13

peroxisomes

Answer 13

• single bound membrane organelles
• contain catalases (redox enymes)
• catalyse decomposition of hydrogen peroxide into water and oxygen
• catabolism of long chain fatty acids, bile and intermediates (in liver)
• beta-oxidation via peroxisomal beta-oxidation system
• fatty acid oxidation: energy production
• detoxification of the body

Question 14

cells with lots of peroxisomes

Answer 14

• immunity cells
• hepatocytes

Question 15

cells with lots of mitochondria

Answer 15

• muscle cells
• spermatozoa
• epithelia

Question 16

mitochondria

Answer 16

• all cells except blood cells and terminally keratinocytes
• number, shape are often characteristic for cell types
• variety of shapes: spheres, rods, elongated filaments, coiled structures
• 1000-2000 per cell (30 000 ovocytes)
• lamellar: Kreb’s cycle: respiration
• tubular cristae: lipid metabolism
• ATP synthase complex and electron transport chain in inner membrane generate gradient to produce ATP
• Ca2+ storage and release
• apoptosis control
• localisation meets the need for local ATP production: sperm tail, striated duct of salivary gland, skeletal myofiber, along microtubules

Question 17

mitochondria input and output

Answer 17

• krebs: 6 NADH, 2 FADH= 24 ATP
• glycolysis: 2NADH + 2 ATP = 8 ATP

Question 18

mitochondrion origin

Answer 18

• evolutionary hypothesis: gradual evolution from reticulum thru functional cloning of existing one
• endosymbiotic hypothesis

Question 19

microscopy techniques to visualize mitochondria

Answer 19

• fibroblast: phase contrast
• Normarsky: differential interference contrast (DIC)
• hepatocyte: hematoxylin
• epithelial cell: mitotracker

Question 20

intercellular mitochondrial transfer

Answer 20

• TNTs: tunneling nanotubes or microvesicles
• donator and recipientor
• from PC12 cells to PC12 cells
• from Astrocytes to neurons
• from bone-marrow derived stromal cell to pulmonary alveoli
• from mesenchymal stem cells to somatic cells

Question 21

mitochondria diseases

Answer 21

• class of diseases causes muscle weakness and neurological disorders due to mito malfunction
• worn out mito may be important for aging
• primarily affects children but adult onset becoming more common
• brain, heart, liver, skeletal muscles, kidney, endocrine, respiratory

Question 22

pompe disease: glycogenosis

Answer 22

• neuromuscular disorder with autosomal recessive transmission
• lysosomal acid a-glucosesidase (GAA) due to GAA gene mutation
• accumulation of glycogen in lysosomes
• failure to dispose of glycogen in muscle reserves: accumulation
• The impairment of the autophagic‐lysosomal pathway in Pompe disease results into accumulation of dysfunctional mitochondria and defective clearance of reactive oxygen species (ROS), thus leading to increased oxidative stress.

Question 23

tissue homeostasis: balance

Answer 23

• more cell death: neurodegeneration, immunodeficiency, infertility
• more new cells: cancer, autoimmunity

Question 24

two types of cell death

Answer 24

• apoptosis: programmed cell death
• necrosis: unprogrammed cell death, injury
• autophagic death

Question 25

apoptosis

Answer 25

- active, genetically determined process - mitochondria and ionic pumps keep working, providing energy for the process - junctions break, chromatin condenses near nuclear periphery - nucleus, cells are fragmented into membrane bound- enclosed apoptotic bodies - bodies phagocytosed by neighbouring cells and roving macrophages

Question 26

uses of apoptosis

Answer 26

- embryonic morphogenesis - removal of dangerous cells (killing by immune effector cells) - regulation of cell number: : of viability by hormones and growth factors

Question 27

apoptosis early events at ultracellular level

Answer 27

- cell shrinkage - budding - cytoplasm condensation - nuclear fragmentation - chromatin condensation beneath the nuclear membrane (picnosis) - fragmentation of fibrillar nucleolus (karyorhexis)

Question 28

necrosis

Answer 28

- cell death mediated by signal transduction from receptor-interaction serine/threonine kinase (RIP)1 to RIP3 - trauma - cells and organelles swell - chromatin condenses - membrane compromised: fluid rushes in - dissolution of cellular structures - cell lysis - invasion of phagocytic cells - inflammation

Question 29

necrosis: early events

Answer 29

at ultrastructural level - cell swelling - mitochondria swelling: loss of cristae - ER swelling - lysosome rupture - organelle disruption

Question 30

necrosis: morphological hallmarks

Answer 30

- cytoplasm: eosinofilic - nucleus: fragmentation: karyorhexis - whole cell: cell detachment, swelling and leakage, blebs, fragmentation

Question 31

signalling pathways for promoting necroptosis

Answer 31

- cytokines such as TNF and Fas ligand bind to their receptors - causing their trimerization and recruitment of adaptor proteins - procaspase-8, RIP1 and other proteins activating caspase-8 - c-8 proteolyzes RIP1 and other substrates to promotre apoptosis - RIP1: receptor-interacting serine/threonine kinase - MLKL: pseudokinase mixed lineage kinase domain-like ------- - if c-8 not activated: RIP1 is activated by phosphorylation recruiting RIP3 - RIP1 phosphorylated RIP3 causing recruitment of MKLK which is then phosphorylated by RIP3 - leads to oligomerization of MKLK: binds to phosphoinositides in membrane to form a pore for Na+ and water to come in causing swelling ------- - can also result from activation of toll-like receptors (TLR) like TLR3 and 4 - RIP3 activated through the binding of an adapter protein to the TLR - RIP1 independent mechanism - RIP3 activates MKLK which then oligomerizes and forms pores leading to membrane rupture

Question 32

signalling pathways promoting pyroptosis

Answer 32

inflammasome - pyroptosis eliminated microbial pathogens within and outside cells

Question 33

necrosis and apoptosis compared

Answer 33

A: - gene driven - chromatine condensation, nucleus, fragmentation, cell shrinkage - phagocytisus of remaining apoptotic bodies by neighbours N: - stochastic, triggered by external factors - membrane disruption, cell swelling - cell explosion and cell contect dispersion (inflammation)

Question 33

signaling pathways promoting ferroptosis

Answer 33

- triggered by lipid peroxidation - GPX4 - also necessarry is the disruption in iron hoeostasis - lipids containing unsat fatty acids are directly oxidised by molecular oxygen