Mitochondria health and disease Flashcards
Mitochondria info
-belived to have evolved from symbiotic bacteria
-contain own genome
-in humans contains 37 genes
-inherited manually
-13 of which encode subunits of respiratory chain complexes
-Nuclear genes encode most of mitochondrial proteins
-Amazing synchrony as nuclear and mitochondrial gene transcription/translation coordinates to synthesise mitochondria
Make up of mitochondria?
-Outer mitochondrial membrane (OMM)
-Inner mitochondrial membrane (IMM)
Matrix - contains many catabolic enzyme systems e.g citric acid cycle, beta-oxidation, pyruvate dehydrogenase, also has DNA, ribosomes, ions, metabolites
What are mitochondria constantly doing?
-Constantly dividing - fission
-Constantly coming together - fusion
-Being degraded when damaged or non functional - mitophagy
-no. of mitochondria in a cell and no. of cristae in mitochondria can change depedning on metabolic need
How are mutations in mitochondrial genome inherited?
Maternally inherited
Examples of mutations in genes encoding mitochondrial proteins?
- Leber hereditary optic neuropathy (LHON)
-degeneration of retinal cells - vision loss
-due to missense mutation in mitochondrial genes that encode subunits of Complex I - Leigh disease
-neurological and psychomotor dysfunction
-due to mutations in both mitochondrial and nuclear genes that encode proteins for complexes of mt chain especially Complex IV - MELAS
-mitochondrial encephalopathy with lactic acidosis and stroke like episodes
-most common cause is mutations in mitochondrial genes encoding tRNA necessary for synthesis of mitochondrial proteins and also cause of MERFF - MERFF
-myoclonic epilepsy with red ragged fibres
-skeletal muscle has abnormal shaped mitochondria w crystalline deposits
What affects can ROS that is produced by the mitochondria have?
-Low levels can be beneficial and cleared by effective antioxidant responses
-but if electron transport not correctly coupled to ATP production and O2 consumption ROS can be overproduced
-ROS very interactive bind to proteins/enzymes lipids and nucleic acids causing them to malfunction
-cause oxidative stress - defective mitochondrial func - defective cell func - cell death in aging and diseases of aging
What is released from mitochondria that activates a signalling pathway and causes cell death?
Cytochrome C
What metabolic rewiring can oncogenes cause?
-Disrupt OXPHOS
-Promote aerobic glycolysis
-Uncouple electron transport from ATP synthesis
-use mitochondrial metabolism for biosynthesis
What effect can pathogens have on mitochondria?
Can manipulate mitochondrial metabolism and OXPHOS to promote infection
-metabolic/ mitochondrial bioenergy response to pathogens important in effective immune response and reducing inflammation
-when mitochondrial metabolism and dynamics are impaired, damaged mitochondria can be dangerous and cause inflammation
Mitochondrial defects in Parkinsons disease?
-Defects in mitochondrial function central to Parkinsons disease
-Complex I activity is impaired and defects in ATP synthase reported
-Risk genes whose loss of func causes Parkinsons regulate major mitochondrial functions including effective mitochondrial fission/ fusion and mitophagy
What is MPTP?
-Mitochondrial toxin
-Neurotoxin that caused rare permanent very rapid symptoms of Parkinsons when injected by a number of people in the 1980s
-accidentally produced during the illicit manufacture of MPPP, synthetic opioid drug
