Lecture 17: The Genetic System of Mitochondria Flashcards
Mitochondria are dynamic and make up ___ % fo cytoplasmic volume. They are even often associated with microtubular cytoskeleton. They are able to move up and down the microtubules and interact directly with the ___ in a unique fasion
20%, ER
Mitochondria are much less dynamic in ___ cells
- high energy cells
- They are much mor fixed
- they can pack tightly between myofibrils (cardiac muscle) and around the flagellum of sperm cells
evolution of mitochondria
from fermenting bacteria to photosynthesis- to cellular respiration
in the reducing atmosphere bacteria where fermenting bacteria but then when oxygen increased in the atmosphere bacteria split and formed the
cyanobacteria (which later became chloroplasts), and purple nonsulfur bacter such as alpha proteobacteria (which later became mitochondria)
Mitochonrial DNA is what shape
circular
do mitochondria still require protiens form the cytosol
yes
when healthy what is the shape of mitochonria
long and slender
(this makes sense because it increases the surface area nd thus increases the ability for electron transport)
What cytoplasmic proteins can aid in the process of mitochondrial fission
Dynamin-1 (not this does require GTP)
Does it take more energy to fuse the inner or outer membrane of mitochondria
It takes more to fuse the inner membrane
Fusion of mitochondria is often used in times of stress to save some mitochondria but explain hwo it can be used in times of healthy bacteria
fusion can occur to increase the surface area of Mitochondrion. Then if one spot is damaged it is fused out and mitophagy occurs. (thus both a fusion and fission event can occur in times of stress)
How many base pairs is human mitochondrial DNA
16,569bp
Are there DNA repair mechanisms in the mtDNA
no
what is largely coded for in the mtDNA
tRNA (20 transfer amino acids)
changes in mt tRNAs have been linked to over 200 disease states and often these mutations prevent
tRNA aminoacylation
Mitochondrial DNA is inherited by
maternal side
Accumulation of ROS-generated by the respiratory chain-can cause
mitochondrial DNA damage
ROS increase with
age
The _____ is particularly susceptible due to the high amount of “combustion”
- brain (because it uses 20% of your glucose and O2)
Parkinson’s disease is treated with
L-DOPA, agonists
Parkinson’s disease is a result of loss of dopamine signaling in the midbrain due to the
diminishment of the substantia nigra this can also lead to memory loss and demntia associated with the progression of PD
Give an example of a genetic correlation that is found in 15% of Parkinson’s disease patients
alpha-synuclein
Parkinson’s disease pathology
- Loss of dopaminergic neurons
- formation of lewy bodies?
- alpha-synuclein becomes insoluble and aggregates
- similar to beta-amyloid in AD
- seen early in olfactory bulb without symptoms
- alpha-synuclein becomes insoluble and aggregates
- Neurofibrillary tangles and phospho-Tau
- also similar to AD
- usually seen when a person reaches stage of dementia
Etiolgy of Parkinson’s disease and links to mitochondrial integrity
- Familial PD is caused by mutations
- genes identified by linkage analysis
- autosomal recessive or dominant manner
- Sporadic PD is more complex
- both genetic susceptibility and environmental factors contribute
- both genetic and envrionmental factors influence various mitochondrial aspects, such as bioenergetics, dynamis, transport, and quality control
increasing Nampt as therapy for PD alters ___, ____, ____, and ____ levels in skeletal muscle of aged rats
- SIRT1
- SIRT6
- NAD
- NAMPT
- (note that a glucose restriction increases Nampt mRNA)