Week 12 Flashcards
(96 cards)
What is the electron transport chain?
Theelectron transport chainis a collection of membrane-embedded proteins and organic molecules, most of them organized into four large complexes labeled I to IV.
What happens in the electron transport chain to produce energy?
As the electrons travel through the chain, they go from a higher to a lower energy level, moving from less electron-hungry to more electron-hungry molecules.
Energy is released in these “downhill” electron transfers, and several of the protein complexes use the released energy to pump protons from the mitochondrial matrix to the intermembrane space, forming a proton gradient.
In the inner mitochondrial membrane, H^++start superscript, plus, end superscriptions have just one channel available: a membrane-spanning protein known asATP synthase.
Conceptually, ATP synthase is a lot like a turbine in a hydroelectric power plant. Instead of being turned by water, it’s turned by the flow of H^++start superscript, plus, end superscriptions moving down their electrochemical gradient.
As ATP synthase turns, it catalyzes the addition of a phosphate to ADP, capturing energy from the proton gradient as ATP.
What is unique for mechanism and patterns of inheritence?
Inheritance of cytoplasmic genomes is distinct from nuclear genomes (in animals they are mitochondrially inherited)
Where are cytoplasmic genomes are located?
Mitochondria (animals, plants and fungi)
Chloroplasts (plants)
What is required for biogenesis of functional mitochondria?
It is dependant on co-ordinated expression of nuclear and cytoplasmic genomes
What are the different genes in the mitochondria?
2 rRNAs
22 tRNAs
13 protein genes
What happens if there a mutation in mtDNA?
They are mostly lethal
What is the relationship between mt genome and mt rRNAs?
Mitochondria have their own ribosomes but while mitochondrial rRNAs are encoded in themitochondrial genome, the proteins that make up mitoribosomes are encoded in thenucleusand assembled by cytoplasmic ribosomes before being implanted into the mitochondria
55S (39S/28S) and 80 proteins as opposed to the 80S eukaryote mitochondria
How did they demostrate the maternal inheritance of animal mtDNA?
The mtDNA of X(Xenopus). laevis and X. borealis can be distinguished at the molecular level.
Reciprocal crosses were performed and the mtDNA genotype of the F1 progeny was determined.
These analyses demonstrated maternal inheritance of mtDNA in Xenopus.
Why is mitochondrial DNA inherited maternally?
Differences in gamete size means zygotes would receive very few paternal mitochondria.
Paternal mitochondria do not normally enter the egg (chemically marked and degraded if they do).
Human eggs contain c.2000 mitochondria.
What is the structure of mitochondrial genome?
Thehuman mitochondrial genomeis a circular double-strandedDNAmolecule of about 16kilobases
As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats
How are mitochondrial genes transcribed?
Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs
Where are most genes for mitochondria encoded?
Most proteins necessary for mitochondrial function are encoded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion
NADH dehydrogenase
Cytochrome
Part of the electron transport chain for making ATP
What is different about the genomone DNA and mitocondrial DNA sequence?
Researchers observed differences in mitochondrial proteins predicted from the gene sequence
UGA is stop codon in universal code but codes for Trp in mt code
AGG/AGA is Arg in unviversal code but codes for stop codon in mtDNA code
What can variations in the genetic code show?
Determine relative evolutionary proximity to other species
When did the first mitochondria appear?
Around 1.6 bya originating as an aerobic prokaryote in a symbiotic relationship with anaerobic eukaryote
What is another cause for mitochondrial disorders outside of mitochondrial mutations?
Mitochondrial disorders can be a consequence of nuclear gene mutations that encode mitochondrial proteins. These mutations show strictly Mendelian patterns of inheritance (usually autosomal recessive). In total over 200 genes have been identified
What is the overview of mitochondrial diseases?
Several diseases of the human nervous system are caused by mutations in the mitochondrial genome which shows a distinct pattern of inheritance.
Mutations are passed from mothers to children (maternal transmission).
Symptoms vary due to heteroplasmy
What is heteroplasmy?
Variation in the types of mitochondria (some mutant some wildtype)
How does heteroplasmy cause variation of symptoms?
Different split of mitochondria therefore some oocytes have more mutant mitochondira which causes high levels of symptoms also the opposite could occur with low level symptoms
What is the Charlie Gard case?
The legal battle that centered around Charlie Gard captured international attention and offers of support from Donald Trump and the Pope
Disease is called infantile onset encephalomyopathy mitochondrial DNA depletion syndrome (MDDS).
What are the symptoms of MDDS?
MDDS causes progressive muscle weakness and brain damage
What causes MDDS?
Autosomal recessive nuclear mutation in the RRM2B gene (Chromosome 8)
RRM2B encodes a ribonucleotide reductase enzyme
It is required for normal mtDNA synthesis and repair
These parents must both be heterozygous carriers of the nuclear mutation
Where can mitochondrial DNA mutations impact?
They can affect everywhere:
Heart- Cardiomyopathy
Pancreas- Diabetes
Brain- Seizures
Skeletal muscle- Myopathy
