Mitochondria and Disease Flashcards
2 highly specialized membranes
- Mitochondrial inner membrane
2. Mitochondrial outer membrane
Mitochondrial outer membrane
- separates from the cytosol
- contains many porins
- permeable to certain molecules
Mitochondrial inner membrane
- highly impermeable
- contains large amounts of cardiolipin
Mitochondrial mobility
Mitochondria are highly mobile, move along microtubule network and accumulate at energy-demanding parts of the cell
Differentiating cells
Numerous morphologically and functionlly distinct mitochondria
Metabolic activity cells
- dissipation of energy
- development
- defense against aging
- mitochondria can form a mitochondrial reticulum/network
Mitochondrial matrix
Citric acid cycle generates high energy electrons through oxidation of substrates
Mitochondrial inner membrane
Electrons are donated via NADH to the respiratory chain
Glycolysis
Eectron carriers transport electrins to reactions in the mitochondria
Biosynthesis
Production of key intermediates for biosynthesis of nucleotides, lipids, gluthione etc.
- ananolic reaction
Degradation
- amino acid degradation (urea cycle)
- lipid degradation
- catabolic reaction
Virtually all mitochondrial proteins are
- encoded by genes in the nucleus
- synthesized on cytosolic ribosomes
- imported from cytosol into mitochondrion
- protein transport is unidirectional
Initial steps in mitochondrial protein import
- binding of signal sequenxe to receptor
- chaperones and other associated proteins are removed
- unfolded polypeptide chain enter TOM complex
SAM
Sorting and assembly machinery
Mim1
Supports assembly if -barrel protein
Mdm
Mitochondrial distribution and morphology
Mmm1
Maintenance of mitochondrial morphology
Kearns-Sayre syndrom (KSS)
External ophthalmoplegia, cardiac conduction defects, and sensorineural hearing loss
Peber hereditary optic neuropathy (LHON)
Visual loss in young adulthood
Myoclinic epilepsy and ragged-red fibre (MERRF)
Progressive myoclinic epilepsy, clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fibre
Leigh syndrome (SNEM)
Seizures, altered states of consciousness, dementia, ventilatory failure
Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
Dementia, in addition to symptoms described in the acronym
Myoneurogenic gastrointestinal encelopathh (MNGIE)
Gastrointestinal pseudo obstruction, neuropathy
Heteroplasmy
Mix of multiple mtDNA copis per mitochondrion of which some mutated
Threshold expression
Number of affected mitochondria have ti reach certain level before mitochondrial disease clinically apparent
Mitotic segregation
Daughters and sons inherit this mix, will be healthy unless process mitotix segregation result in majority of defective mitochondria in particular tissue
Tim22 complex
Promotes insertion of multipass membrane proteins into the inner membrane
Diagnosis of mitochondrial disease
- Metabolic testing
- muscle testing
- genetic testing
What do mitochondrial metabolites do?
- signaling
- regulate cellular gene expression
Where is mitochondrial genetic system located?
In the mitochondrial matrix
