mitochondria

Question 1

Mitochondria are composed of bigenomic proteins

Answer 1

Mitochondrial-nuclear cross talk is essential for mitochondrial functions including the correct synthesis, import/folding/assembly, and functioning of respiratory chain enzymes

Respiratory subunits 1, 3 , 4, 5 is made by both mitochondrial and nuclear subunits

Question 2

Mitochondrial DNA

Answer 2

Each mito has 2-10 copies of mtDNA lots of cytoplasmic inheritance

mtDNA is maternally inherited

mtDNA replication is NOT dependent on cell division

mtDNA undergoes replicative segregation during mitosis and meiosis

mtDNA has a mutation rate 10-20x higher than that of nuclear DNA

mtDNA mutation has a threshold expression that when crossed the cell/organ will suffer

Question 3

Role of nuclear genome in mitochondrial biogenesis and nuclear mito interactions

Answer 3

nuclear DNA:
cooperates with mtDNA in synthesis and assembly of multisubunit oxidative phosphorylation subunits

encodes all components of protein import machinery

encodes transcription factors for mtDNA transcription, replication and for proteins that target the mito

Question 4

Mitochondrial pathologies

Answer 4

mutation in different genes can cause the same syndrome, and disease can occur from mutations in either mt or nu DNA

3 possible sources of mutations: nuclear DNA (mendelian inheritance), mtDNA (non mendelian inheritance maternally inherited), X linked

mtDNA mutations:
mtDNA attached to IMM (source of ROS), mtDNA lacks protective histones, mtDNA has a limited repair system

missense mutations: AA substitutions (LHON)
biogenesis mutations: tRNA point mutations affects protein synthesis (MERRF and MELAS)
insertion-deletion: usually no family history (KSS, and PEO),
copy number mutations

Question 5

how are nuclear encoded proteins incorporated

Answer 5

> 90% of mitochondrial proteins need to be imported from nuclear genes

they have a targeting sequence or presequence (rich in basic, hydroxylated AA at N terminus), can form amphipathic structures, cleaved by specific peptidases in the mito

cytosolic factors (Hsp70): help unfolding need ATP

Question 6

major pathways affecting mito biogenesis

Answer 6

decrease in dG (low ATP) acitvates glycolysis and oxidative phosphorylation and AMP Kinase

AMPK inhibits ATP consuming reactions (protein synthesis, glycogen syn, FA syn, sterol syn) and activates ATP generating reactions (glycolysis, glucose uptake, FA oxidation, mito biogenesis)

it inhibits mTOR and activates PGC1 A (which activates mito genes)

Question 7

AMP kinase helps integrate energy demands with cellular metabolism

Answer 7

AMPK is the master metabolic regulator

it maintains nucleotide pools over a wide range of Energy demands

AMP stimulates glycogenolysis and glycolysis

AMPK remains inactive until its phosphorylated

Question 8

mitophagy

Answer 8

removes damaged goods

nuerodegenerative diseases

Question 9

Apoptosis is mediated at mitochondria

Answer 9

Apoptosis is important during development and in fighting viral infections

Misregulation of apoptosis causes or contributes to a large number of disease

Regulation occurs at several steps but comitted step is the release of CYT C

Bcl 2 proteins control cyt c release
Bcl 2 proteins come in 2 flavors pro apoptotic and pro survival

Pro apoptotic (Bax. Bak) 
Pro survival : Bcl2, Bcl Xl, Mcl 1 A1 Bclw: make a channel to release cyt C

Question 10

Mitochondrial dysfunction factor in neurodegenerative disease

Answer 10

Parkinsons, huntingtons, Alzheimers, ALS

mtDNA: mutation do not appear to be primary cause of disease