2.7 Structure and origin of mitochondria
What is all eukaryotic cells dependents of?
All eukaryotic cells are decedents of a single cell that has absorbed bacteria with oxidative phosphorylation capacity
What is apoptosis? What do it require to be expressed?
Apoptosis is programmed cell death requiring gene expression, proteosynthesis, and ATP
What protein is important in the outer membrane of mitochondria, and what is it important for?
Bcl protein is important in the outer membrane of mitochondria and is important protein in regulation of apoptosis.
What types of tissues are most related to mitochondrial disease?
Heart and nerve tissues (brain, retina) are most related to mitochondrial diseases.
What is the basolateral labyrinth function, and how is it able to work?
In the basolateral labyrinth transfer of water and ions using Na/K ATPase with high consumption of ATP.
What can we find in the intermembrane space?
In the intermembrane space we can find proapoptotic proteins, cytochrome C and lot of protons
What type of bacteria has mitochondria developed from?
Mitochondria has developed from the bacteria rickettsia
What does the bacteria mitochondria contribute with?
The bacteria mitochondria contributes with producing ATP to the host cell and the host delivers substrates to it. They live in mutual symbiosis
How does the cell treat damaged mtDNA or damaged mitochondria?
The cell is able to recognize and destroy mitochondria with defective mtDNA or trigger apoptosis on the whole cell.
Where does the inner membrane of mitochondria originate from?
The inner mitochondrial membrane originates from the prokaryotic cell.
What is the reason for mtDNA is so small?
The reason for mtDNA is so small is is because of its genome (99% of proteins for mitochondria) codes have moved into the nucleus of the host cell, making the mitochondria nucleus dependent and unable to live independently, 600-1000 mitochondrial proteins are encoded by nuclear of the host cell.
Can antibiotics harm mitochondria? (explain)
Yes, since mitochondrial ribosomes resemble bacterial ribosomes, which means that some antibiotics targeting bacterial ribosomes may also affect the mitochondria.
Which cells contain the most mitochondria? Give example on amount in three cell types
Active cells contain most mitochondria Hepatocytes 800 (functional cell of liver) Oocytes up to 100 000 (immature ovum) Cardiomyocytes up to 30-40% of their volume (muscle)
How much percentage of the outer mitochondrial membrane is made up from proteins and lipids?
Almost 50% of the outer mitochondrial membrane is made up from proteins, and 50%lipids.
What make sure proteins remain unpacked, so they can be transported through the mitochondrial membrane?
Chaperons make sure that proteins remain unpacked so they can be transported through the mitochondrial membrane
How is the structure of mitochondria?
Mitochondria are a membrane semi-autonomous (semi-independent) organelles They have two membranes inner (bent) and outer (smooth) intermembrane space between the membranes. Inside the inner membrane is the mitochondrial matrix The size of mitochondria is 0,5-1 micrometer wide and 3-5 micrometer long. The membrane thickness is 6-8nm and intermembrane space between them is +-20nm Microtubules move towards where they are needed, which are located to surrounding places with high ATP consumption. The microtubules are usually concentrated around the nucleus of mitochondria or basolateral labyrinth
How does mitochondria reproduce them self?
Mitochondria reproduce exclusively asexually
How can we diagnose mitochondrial disease? How common is it?
Mitochondrial diseases usually have heteroplasmy that means there is presence of mutated mitochondria with different mtDNA than the healthy ones. It causes variable symptoms, the reason for this is different distribution of mutant mitochondria throughout the body , symptoms/consequences of disease would depend on where the mutant mitochondria are located. 1: 4000
Is mitochondrial mutation disease variable, and why?
Mitochondrial mutation diseases are most variable spread, since there are several tens of copies of mitochondrial DNA and at the same time we have tens of thousands of copies of mitochondrial DNA in the cell.
What are the mitochondrial theories of aging?
Mitochondrial theories of aging are: Mitochondria naturally forms oxygen radicals that may damage mtDNA or host cells DNA. Accumulation of mutation in mtDNA with age would gradually decrease the function of mitochondria and respiratory complexes. Mitochondrial function impairments (abnormality) affects long-lived cells like neurons, cardiomyocytes, and muscle cells.... Consequences are heart failure, muscle weakness, diabetes mellitus, dementia, neurodegeneration
What does the mtDNA code for?
The mtDNA codes for 37 genes, in this gene we would find 13-14 proteins for the respiratory chain, and encodes 2 rRNA, 22 tRNA.
What codes for repository chains does the mtDNA contain?
The mtDNA codes for this units in respiratory chain: 7 subunits for complex I 1 subunit for complex III 3 subunits for complex IV 2 subunits of ATP synthase
How many base pairs (bps) does mtDNA have and how does the mtDNA look like in structure?
The mtDNA has a structure of double-helix DNA that contains no introns, and is 16,5kbps (16 500 bps)
What enzymes can be found in outer mitochondrial membrane?
The outer mitochondrial membrane contains few enzymes of fatty acid metabolism and phospholipids
How does the passage in outer membrane work and what enters?
The passage of outer membrane works by many porins channels that allows molecules pass through the membrane As a result, outer membrane non selectively permits all molecules smaller than 10kD (10 000daltons)
What is the name of the external and internal complexes of translocators of proteins in mitochondrial membrane?
Tom and Sam complexes are the external (outer membrane) Tim 23 and Tim 22 complexes are the internal (inner membrane)
What does Tom, Sam, Tim 23 and Tim 22 do?
Tom complexes (transporter of outer membrane): gets proteins into the intermembrane space Sam complexes: is for proteins to remain integrated into the outer mitochondrial membrane Tim 23 complex ( transporter of inner membrane): pushes proteins from the intermembrane space into the mitochondrial matrix. Tim 22 complex: Integrates proteins from intermembrane space into the inner mitochondrial membrane
What are the hypothesis of the connection with eukaryote and mitochondria happened and explain them?
1. The first hypothesis states that eukaryote cells developed first and then symbiosis occurred with mitochondria. 2. The second theory is that entry of mitochondria into the cell resulted in eukaryotes, but some eukaryotes organisms do not have mitochondria, or just residues of it.
Name 2 mitochondrial diseases and what happens?
DAD (diabetes and deafness) is caused by mutated leucine gene synthesis which causes abnormal proteins that damages the hair cell in ears and pancreatic beta cells. LHON (Leber's hereditary optical neuropathy) will begin in middle age with optic nerve dying and end with complete blindness, this can be caused by multiple mutation in complex I and this causes the mitochondria to not work all and their ATP production is not enough for powerful and energy intensive nerves.
What is one of the main causes of cell death and why?
Defects in membrane permeability in mitochondria or membrane damage in mitochondria is one of the main causes of cell death. The initial (first) phase of cell damage is disruption of the membranes, mitochondrial ability to selectively permeability is impaired (weakened), this harms ATP production, leading to ATP deficiency, non-functional membrane pumps and cell swelling.
What can insufficient (utilstrekklig) activity of mitochondria lead to?
Insufficient activity of mitochondria can leads to transmission of disorders and thus to cell edema (hevelse/hovenhet/abnormal collection of fluid)
Where does the proteins to mitochondria get produced?
Most of the proteins to mitochondria is imported from the cytoplasm, which means they are synthesized on ribosomes in the cytosol. Some are made in the mitochondrial matrix which is 13-14 proteins.
How is mutation in mitochondria classified?
Mutation in mitochondria is classified according to where they occur
How is mutation in mitochondria inherited?
Mutation in mitochondria is only inherited by maternal inheritance (1: 4000), because parental mitochondria is not passed on
What type of important complex is found in mitochondrial inner membrane?
The complex we can find in the inner mitochondrial membrane is the respiratory chain complex, where ATP synthase forms elemental bodies on the inner mitochondrial membrane.
What are the fold of the inner mitochondrial membrane called? How do they look like in steroid producing cells?
The folds of inner mitochondrial membrane are called cristae, and in cells producing steroid hormones cristae is modified and forms tubules
How selective is the inner mitochondrial membrane?
The inner mitochondrial membrane is almost impermeable and very selective, everything except for small uncharged molecules need a carrier
What is the inner mitochondrial membrane composed of?
The inner mitochondrial membrane is composed of 75-80% proteins and 20-25% phospholipids. It has no cholesterol. the phospholipids are cardiolipin (4 fatty acid, 2 phosphoric acid, 2 phosphatidic acid) that helps with elasticity. This make it very poorly permeable. It has 50 different transporters for 50 different chemicals.
How is the composition of of intermembrane space?
The intermembrane space has a similar composition to cytosol (much less protein concentration than the matrix) = less dense than the matrix
What is the membrane potential between the inner membrane and intermembrane space?
The membrane potential between the inner membrane and intermembrane space is -150mV to -180mV. Fun fact: If we increased the intermembrane space form +-20nm to 1 meter the membrane potential would increase to 30 000 000V which equivalent to a lightning strike voltage.
How does the mitochondria contribute to the apoptosis of the cell?
The mitochondria contributes by releasing of pro apoptotic factors from the intermembrane space, which interrupts the supply of energy to the rest of the cell and overproducing ROS (reactive oxygen species)
Where is mitochondrial matrix located?
The mitochondria matrix is located inside the cristae.
What is the mitochondrial functions?
The mitochondrial functions are production of ATP by oxidative phosphorylation, Krebs cycle, beta-oxidation, ketogenesis, steroid synthesis, ornithine cycle (urea cycle), gluconeogenesis, iron and calcium metabolism, regulation of intracellular calcium, triggering of apoptosis or necrosis of the cell, synaptic plasticity and thermogenesis.
What does the mitochondrial matrix contain?
The mitochondrial matrix contains enzymes of Krebs cycle, beta-oxidation of fatty acids and ornithine cycle (urea cycle), various nucleotide coenzymes, inorganic ions (Ca), mtDNA, relevant tRNA and mRNA, mitochondrial ribosomes, chaperons and chaperonins.
What is the mitochondrial matrix?
The mitochondrial matrix is a gel like substance because of its high protein concentration at 500g/L
Whats different form the cell membrane and mitochondrial outer membrane?
The mitochondrial outer membrane don't contain cholesterol
Why is mitochondria dependent on the host cell?
The reason for mitochondria is dependent on the cell is that most of its genome has moved into the cell nucleus of the host cell, making mitochondria unable to live without the host cell
What is the theory of mitochondria called?
The theory of how mitochondria ended up in the cell are is called endosymbiotic theory
What can trigger apoptosis?
The things that can trigger apoptosis to be expressed is response of apoptotic signal, stress and cell damage.....
Where can you find translocators for the proteins in mitochondria?
We can find the translocators on the inner and outer mitochondrial membrane
What type of therapy works on mitochondrial diseases? Why docent CRISPR work as treatment?
With help of classic medicines there is little help, and very difficult to treat. Only possibility is of so called mitochondrial transplantation, but the child would then have 3 parents, first from egg with no nucleus, second from nucleus of egg, and third the sperm, but this method is only legal in UK. Unfortunately CRISPR method don't work on mitochondrial DNA because it won't be able to pass through the inner membrane of mitochondria.
Can the mitochondria produce own molecules encoded by its own gene?(explain)
Yes, since the matrix of mitochondria contains also a proteosynthetic apparatus and 70S ribosomes that can produce molecules encoded by mitochondrial DNA.
What do we call mitochondrial DNA?
mtDNA
How do we inherit mtDNA?
mtDNA is only inherited from maternal, because all the mitochondria is in the egg cell.
Which is mutates faster nuclear genome or mtDNA and why?
mtDNA mutates faster than nuclear genome, since it is more vulnerable to mutation accidents than nuclear genome.