Lecture 1

• What is a disease?

  Consequence of a failure of homeostasis
• What is homeostasis?


  The maintenance of equilibrium in the body despite changes in the internal/external environment
• What is allostasis?


  The body's ability to maintain a stable physiological environment by adjusting and changing to meet internal and external demands.
• What is allostasis necessary for?

  It is the overall process of adaptive change necessary to maintain survival
• What is allostasis essential for in terms of maintaining equilibrium?

  Allostasis helps maintain homeostasis, and therefore is important for homeostasis maintenance.
• What is aetiology?


  Cause of a disease or condition
• What is pathogenesis?


  The process by which an infections leads to disease
• What is pathology?


  The study and diagnosis of disease
• Describe the mitochondria:


  Bacteria-like organelle which is double membraned and has its own DNA
• What is the cytosol?


  Fluid component which contains dissolved nutrients to help break down waste products
• What is the lysosome?


  Specialised forms of vesicles that contain hydrolytic enzymes to break down waste materials in cells
• What is the process carried out by the lysosome called?

  Autophagocytosis
• What does the Golgi apparatus do?

  Post-translational modification of proteins and packaging them into vesicles
• Where are new proteins required at the plasma membrane or other places synthesised?

  Rough endoplasmic reticulum
• What are the three different sites at which breakdown of protein?

  Lysosomes, proteasomes, peroxisomes
• What is the set point in homeostasis?

  the physiological value around which the normal range fluctuates
• What is ubiquitination?


  post-translational modification that generally directs proteins for degradation by the proteasome or lysosome
• What is poly-ubiquitination?


  it occurs when ubiquitin molecules are attached end-to-end to a single lysine residue on a substrate protein to form a poly-ubiquitin chain
• how is a ubiquitin protein attached to a substrate protein?

  covalently/ isopeptide linkage
• What is the process mitochondria takes to generate ATP?

  oxidative phosphorylation
• What can mitochondria do in terms of cell damage?

  it can sense cell damage and initiate and regulate programmed cell death
• What are two roles of the mitochondria?

  - ATP generation

  - TCA cycle intermediates (lipid protein building blocks

  - apoptosis signals
• What is the origin of mitochondria?

  endosymbiotic origin (bacterial)
• What is mitochondrial DNA more susceptible to and how?

  more susceptible to DNA damage

  - this organelle uses oxygen ---> water (ROS)

  - this environment can give chance to free radicals
• Lack of histone production in mtDNA causes...

  Unlike nuclear DNA, which is protected by histone proteins, mtDNA is not associated with histones. Histones help shield nuclear DNA from damage caused by environmental factors or cellular processes
• lack of repair mechanisms in mtDNA leads to

  no repair mechanisms, means cell can't be repaired, leading to APOPTOSIS
• How man proteins are needed for function of mitochondria?

  13 proteins
• What is the inheritance of the mitochondria?

  matrilineal - inherited from mother
• What is homoplasmy?


  At birth, all copies of mitochondrial genome are identical
• What is heteroplasmy?


  where two or more mtDNA variants exist within the same cell, - normal and mutated - causing mitochondrial disorders
• What does the threshold effect mean in mitochondrial disorders?


  the proportion of mtDNA pathogenic variants must exceed a threshold before abnormality is expressed
• Describe mitochondrial disorders do in terms of energy metabolism:

  they are heterogenous group of rare inherited diseases of energy metabolism
• How does the percentage level of mtDNA pathogenic variants vary?

  - varies between individuals within the same family

  - also varies among organs and tissues within an individual
• What are some disorders caused by pathogenic mtDNA?

  Leigh syndrome and Pearson syndrome
• Describe characteristics of Leigh syndrome:

  affects CNS, progressive loss os mental and movement abilities
• Describe characteristics of Pearson syndrome:

  caused by mutations. makes it hard for cells to make energy
• What is the uncommon name for mitochondrial replacement?

  Three parent baby
• What are the two techniques of mitochondrial replacement?

  maternal spindle transfer or pronuclear transfer technique
• How does pronuclear transfer technique work?

  there is a patient couple with abnormal mitochondria and a donor with normal mitochondria

  - injection of sperm

  - formation of pronuclear zygote

  - nucleus removed from patient couple with abnormal mitochondria and put into cell of donor (donor's zygote is discarded)

  leaves a reconstituted zygote with pronucleus from intending couple and healthy mitochondria from donor
• How does the maternal spindle transfer technique work?

  there is a mother and donor egg

  - the spindle of chromosomes which binds with the chromosomes from the sperm is taken out of the mother's cell

  - the spindle of chromosomes from donor's cell with healthy mitochondria is taken out

  - the spindle is transferred from the mothers to the donor's cell

  leaves a cell with chromosomes from intending mother and father + healthy mitochondria from donor