Mitochondria Flashcards
How many genes does the mitochondria contain?
37 genes, 13 of which encode subunits of the respiratory chain complexes
Nuclear genes encode most of the mitochondrial proteins.
How are mitochondrial genes inherited?
Maternally
How many membranes do mitochondria have?
2 membranes - Outer,(OMM) very permeable. Inner,(IMM) impermeable.
What does the IMM contain?
Highly convoluted with invaginations - cristae containing multiple copies of respiratory chain and ATP synthase.
There are multiple transporter proteins in the IMM, give an example?
Carnitine.
What does the matrix of the mitochondria contain.
Many catabolic enzyme systems:List on diagram (examples: DNA, ribosomes, ions, metabolites , citric acid cycle, beta oxidation, pyruvate dehydrogenase and for amino acid oxidation.
How are mitochondria highly dynamic? Why is this done?
They are constantly dividing by fission - to get rid of damaged mitochondria.
When does a lot of fission happen?
During anabolism
What is it called when mitochondria come together?
fusion
What is it called when mitochondria are being degraded when damaged or non-functional?
Mitophagy, proteins are also degraded by this.
What can differ between mitochondria cell types?
The cell need for high energy demand etc.
Number of cristae can change depending on the metabolic need.
What type of mutations in genes encoding for mitochondrial proteins can cause disease?
Inherited optic neuropathies.
- degeneration of retinal cells (loss of vision)
What causes Inherited optic neuropathies?
Missense mutation in mitochondria genes encoding subunits of complex 1.
Maternal (primarily)and nuclear inherited.
What is Leigh disease?
This is a neurological and psychomotor dysfunction - due to mutations in both mitochondrial and nuclear genes that encodes for protein complexes of mt chain complex IV
What is MELAS?
Mitochondrial encephalopathy with lactic acidosis and stroke like episdoes.
What is MERFF?
Myoclonic epilepsy with red ragged fibres.
MELAS is the most common cause of?
Mutations in mitochondrial gene encoding tRNA necessary for synthesis of mitochondrial proteins and this is also cause of MERFF
What do diseases MERFF and MELAS have?
Defective mitochondrial protein synthesis.
What is visible in the mitochondria of MERFF patients?
Skeletal muscle has abnormal shaped mitochondria with crystalline deposits.
When was the first mitochondrial transplant ?
In 2015 UK approval of embryonic mitochondrial transfer to treat chronic maternally inherited mitochondrial diseases (3 person baby)
What does the mitochondrial transplant consist of?
- chromosomes removed from mutated m mother
- put into healthy donor egg
- egg fertilised
- normal embryo develops, mother chromosome, male chromosome, donor mitochondria.
What are ROS?
These are produced by mitochondria - reactive oxygen species.
Which levels of ROS can be beneficial?
Low levels of ROS can be beneficial and cleared by effective antioxidant responses.
What can happen if the electron transport is not correctly coupled to ATP production and O2 consumption?
ROS can be over produced.
Why are ROS levels so important?
As it is very interactive, ot can bind to proteins/enzyme lipid and nucleic acids causing them to malfunction.
What can high ROS levels lead to?
Oxidative stress leading to defective mitochondrial function - defective cell function or cell death in aging and diseases of ageing such as heart disease, neurodegeneration, type 2 diabetes etc.
What is the role of cytochrome C in apoptosis?
Cytochrome C is released from mitochondria and activated a signalling pathway that causes cell death.
What does apoptosis activate?
Apoptosome which further activates the caspase cascade.
What metabolic systems are present in many cancer cell types?
Aerobic glycolysis and reduced OXPHOS.
Pyruvate to lactate they like to use this - anaerobic glycolysis.
What do many oncogenes cause?
Metabolic requiring that disrupt OXPHOS, promoting aerobic glycolysis and uncouple the electron transport from ATP synthesis.
What do cancer use mitochondrial metabolism for?
For biosynthesis.
Can mutations in the genes encoding protein subunits cause cancer?
Yes of complexes I - IV
What does cancer change in mitochondrial morphology?
Fission/fusion and mitophagy.
Increased rates of mitochondrial fission can promote more rapid cell division.
What can some pathogens do to the immune system?
They can manipulate mitochondrial metabolism and OXPHOS to promote infection.
Why is metabolic/mitochondrial bioenergy response important in the immune system?
Important in producing an effective immune response and reducing inflammation.
What can happen when mitochondrial metabolism and dynamics are impaired?
Damaged mitochondria can be dangerous and cause inflammation.
Age related?
More mitochondrial DNA in blood leading to ?
Death by Sars CoV 2
What is Parkinsons?
This is a slowly progressive degenerative disorder of the central nervous system that impairs the person’s motor skills and other functions.
Which complex is affected along with defects in ATP synthase in neurodegeneration?
Complex 1
What are risk genes?
Loss of pink 1 function which causes parkinson’s has an effect in the balance between fission and fusion and a number of signalling pathways.
What is Parkinson’s disease & MPTP?
A mitochondrial toxin
What was the wrong chemistry involved in the case of the frozen addicts?
MPTP was accidentally produced during the manufacturing of MPPP.
