Mito Genome Flashcards
Outer mito membrane
Permeable to sm molecules
Impermeable large molecules, transport systems
Contains signalling receptors
Intermembrane space
Apoptotic proteins
Inner mito membrane
Transporter proteins
ETC
ATP synthesizing complex
Impermeable to small/large molecules
Mito matrix
Proteins for TCA cycle, lipid oxidation, transamination, mtDNA, mind protein synthesis machinery
What does metabolizing require to occur
Require oxygen and generate ATP
Endosymbiosis
Mito provide ATP, host does all else
Very similar replication to proks
Two genomes-13 polypeptides from mito
2 pathways to mitochondric protein production
and where do proteins go?
from nucleus, rna in cyto, precursor protein, inmported protien
organllele DNA, to rna, to organelle syn protein
Used as inner mito membrane proteins (among other things)
Mito division
Fission and fusion
Similar to bacteria
Change under different physiological conditions
Increasing by double everytime cell divides
Human mito genome
2 rRNA
22 tRNA
13 protein-coding seqs
Can have many copies of DNA
-occurs out of phase of cell cycle
Mito membrane subunits
Most subunits encoded by nuclear DNA%%%%%
mtDNA replisome
Individual mtDNA can replicate individual of cell cylcle
D loop-site of mito dna rep initiation
-also site of transcription promoters
Replication and integrity maintance-nuclear DNA
DNA poly, exonuclease/proofreading, lyase activity (enzymatic DNA repair)
Twinkle-DNA helicase, also acts as primase
DNA pol gamma
Both have mutations that lead to mito disease
tDNA genetic features
very high mutation rate
Maternal inheritance
Bottle neck
Replicative (random) segregation of mito and tDNA
threshold efect
changes with age
High mutation rate
CLose to reactive O2 species
DNA poly has proofreading errores
No introns-all mutations in coding region
Bottleneck effect
Primoridal germ cell has heteroplastic mtDNA mutation
During oogenesis, reduction in ant of mtDNA present
Random samping tells if going to have mutated mito or not mutated
Random/replicative set of mito and mtDNA
mito fusion and fission leads to random dist of mito and mtDNA
Can have mixtures of mutant and normal tDNA in same cell
(different than homoplasmy-all normal or all mutant tDNA)
Threshold effect
Need a certain threshold of ox phos for cell to function (which is different or each cell)
Also need certain amount of mutated mitos to show expression (50%?)
mt changes with age
levels of ox phosphorylation decline
ATP syn drop below threshold, problems result
mutations occur much more rapidly as get older
Mito inhericance
All females with homosplassmic mutation will pass it down, males with homoplasmic will not
Heteroplasmic pt/dups depends on threshold/ bottleneck
-deletions generally not heritable
Different numbers of mutant mito per dif tissues-diseases can vary tremendously-variable expression
2 mechs of mito disease
impair mito protein synthesis
protein coding gene mutation
Mutations in mtDNA are from
Heridary-from mom
Somatic-can be spontaneous in oocyte or early embryo
Can result in free radical damage or from defective mtDNA replication due to mutation in DNA poly gamma
Mito DNA poly?
DNA poly gamma
Mito DNA disease symptoms (4)
Build up of lactic acid if defect is oxidative phosphorylation
Matneral inheritance
Late onset due to accumulation of mtDNA mutations leading to inefficient ox phos
Varability in tissues and among family members (random seg and heteroplasmy)
Leber’s hereditary optic neuropathy
Maternal inheritance (no affected male transmits disease)
Sudden death of optic nerve
80/90% is threshold
mtDNA coded disease
mtTRAnscription
polycistronic precursor mRNA
-codes for ribo RNA and tRNA
2 ribo proteins
most are prob from DNA
mtTRANSLATION
normal codon/anticodon pairing rules are relaxed
- many tRNA molecules don’t even bother with third position DNA
- fewer tRNA needed
Proteins come in and help start/stop translation
Only two ribosomal proteins are made by mito genes-but all tRNA is made from mito genes
Proteins needed for translation-nucelarly encoded
oxphos proteins
Mostly by nuclear DNA
Mito gamma polyermase mutations
MANY DISEASES
Diseases with no RRFs vs with RRF
Leigh Syndrome and Leber sydrome
-problems with energy metabolism
CPEO, KSS, MELAS, MERRF
- ataxia, short, dementia
- —CNS problems
RRF are actually mitochondria
HALL MARK OF MITO DISORDERS (only 1/3 of all mito diseases)
Succinate dehydrogenase and cytochrome d oxidase
RRF proteins
