Lecture II Flashcards
Tonon
How is mitochondrial DNA transcribed?
as a polycystronic unit and the regulation occurs post-transcriptionally (possibly through mitomiRNAs
What are miRNAs?
endogenous small ncRNA that act as post-transcriptional regulators
their expression is tissue-specific
physiologically involved in cell growth, cell proliferation, and apoptosis
pathologically involved in the regulation of different genes and proteins
*they can also be biomarkers for disease
Review the biogenesis of miRNA:
https://www.youtube.com/watch?v=VCgtrtS6pzc
https://www.youtube.com/watch?v=j-zTy6vOP3M
What do miRNAs act as?
translational repressors
*recently also translational enhancers
What are mitomiRNAs?
mitochondrial microRNAs that have different functions in biological and pathological situations
expression is tissue specific
Review the biogenesis and maturation of mitomiRNAs:
https://www.youtube.com/watch?time_continue=1&v=t5jroSCBBwk&embeds_euri=https%3A%2F%2Fwww.tamirna.com%2F&feature=emb_logo
What can mitomiRNAs be involved in?
mitochondrial metabolism
fussion and fission
pathologies: Alzheimer and cardiovascular
What are some different hypothesis on how the mitomiRNAs enter the mitochondria?
specific motif at the 3’ terminal
post-translational modification
PNPase (a ribonuclease)
AGO2 via pores of the outer membrane
P-bodies
PIMILIO1 (RNA binding protein)
How is mitomiRNA isolated?
cerebellar tissue was isolated and homogenized using anti-TOM22 Ab-coated magnetic beads
solution obtains pure mitochondria
How do we remove the outer membrane from isolated mitochondria?
using a digitonin, which is a detergent that creates pores in the outer membrane
What is the last step in the isolation of mitomiRNAs?
using ribonucleases to remove the RNA remaining outside
Is it possible to detect mitomiRNA and AGO2 inside the mitochondria derived from cerebellum?
yes and it is relevant to detect specific targets of mitochondrial DNA encoded proteins that will be regulated so this can be a potential therapy for primary mitochondrial diseases
What uses a lot of ATP and requires a lot of mitochondria?
neurons
What do energy and ion balance link to?
transport
What does ion balance of neurons control?
movement
what can mitochondrial dysfunction lead to?
loss of calcium uptake
increased ROS production
triggering of apoptosis
loss of ATP synthesis
What do mitochondrial dysfunctions mostly affect?
neurons and muscles
Is the mitochondrial network localized or diffused?
it cannot be a network as the axon and dendrites are very thin
a single mitochondria travels along the dendrites and axons and undergo fusion and fission
What are the 3 levels of mitochondrial quality control in mitochondria?
molecular
organellar
cellular
How are the 3 levels of mitochondrial quality control activated?
depends on the entity of the damage
What is different about the mitochondria in terms of the control of the proteome?
they are able to control it themselves
What happens if the quality control system of the mitochondria fails to recover damage?
apoptosis is triggered via the release of cytochrome c from the inter membrane space to the cytosol