Mitochondrial Biology Flashcards
What do mitochondria play a key role in?
apoptosis, calcium metabolism, cellular communication, and stress responses
What does mammalian mitochondrial DNA encode?
- 13 essential protein subunits of the ETC
- 22 tRNAs
- 2 rRNAs
What can the mtDNA copy number be used for?
to estimate mitochondrial content or biogenesis/turnover (it can change depending on the number of mitochondria)
What is the endosymbiotic theory?
- mitochondria descend from a symbiotic relationship between an ancestral eukaryotic cell and a prokaryotic organism
- this provided the host cell with the ability to perform oxidative phosphorylation i.e. more energy production
- over time, most of the genes from the bacterial genome were transferred to the nuclear genome of the host cell through gene transfer and creating the mtDNA
What is the key evidence that supports the endosymbiotic theory?
- double membrane structure – suggests an engulfment process where the outer membrane originated from the host’s plasma membrane
- own DNA and circular genome – similar to bacterial genomes; not enclosed in a nucleus and replicates independently through binary fission
- bacterial-like ribosomes and protein synthesis – can synthesise some of their own proteins, independent of the nucleus
- antibiotic sensitivity – certain antibiotics that inhibit bacterial ribosomes also affect mitochondrial protein synthesis i.e. bacterial origin
What does the intrinsic/mitochondrial pathway of apoptosis involve?
- mitochondrial dysfunction
- release of cytochrome C
- activation of cascade-9 at the apoptosome
What is the apoptosome made up of?
Apaf-1 and cytochrome C
How is Bcl-2 antiapoptotic?
it inhibits the the release of cytochrome C from the mitochondrion and controls mitochondrial membrane permeability
What does caspase-9 do?
activate downstream caspases caspase-3 and 7
How are mitochondria highly dynamic?
they are constantly undergoing fission and fusion to maintain function
Describe fission and fusion
- fission - mediated by Drp1 and allows damaged mitochondria to be degraded by mitophagy and helps with cell division
- fusion - mediated by Mitofusins and enables mitochondria to share contents, promoting metabolic efficiency and repair
What is the role of mitochondria in calcium metabolism?
- act as calcium buffers by sequestering excess cytosolic calcium, which could induce cell death
- calcium storage within the mitochondrial matrix, often as insoluble calcium phosphate complexes
- calcium uptake into mitochondria via the mitochondrial calcium uniporter activates enzymes in the TCA cycle
What happens when an apoptotic insult (stress/damage) occurs?
- excess calcium is released from the ER which leads to mitochondrial overload
- overload triggers mitochondrial membrane to rupture, releasing caspase factors that promote apoptosis
- cell dies due to programmed cell death mechanisms
What are the 4 steps of cellular respiration?
- glycolysis
- TCA cycle
- ETC (inner mitochondrial membrane)
- ATP synthesis (inner mitochondrial membrane)
What is the main role of the TCA cycle?
to regenerate reduced coenzymes (NADH, FADH2) critical for the generation of more ATP via oxidative phosphorylation
Which reactions of the TCA cycle are the most important?
3, 4, 6 and 8
What are the products of one TCA cycle?
1 ATP, 3 NADH, 1 FADH2 and 2 CO2
What are the 9 substrates of the TCA cycle?
- Acetyl CoA
- Citrate
- Isocitrate
- (alpha) Ketoglutarate
- Succinyl CoA
- Succinate
- Fumarate
- Malate
- Oxaloacetate
What are the 4 steps of the ETC?
- NADH and FADH2 generated from the TCA cycle release electrons and H+
- CoQ and cytochrome C carry electrons freed by the complexes
- the 4 complexes generate a H+ gradient
- ATP synthase uses the H+ gradient to convert ADP to ATP
Which complex in the ETC is fully nuclear encoded?
complex II
Why is coordination of nuclear and mitochondrial gene expression key?
to ensure proper ETC assembly and function, and to control mitochondrial stress adaptation
How do mitochondria respond to oxidative stress?
by producing ROS, which act as signalling molecules but can also cause damage if excessive
What is mitophagy?
a selective form of autophagy that removes dysfunctional mitochondria to prevent cellular damage
How does the unfolded protein response (UPRmt) help maintain mitochondrial proteostasis?
by activating stress-response genes in the nucleus (acts in response to broader alterations and requires mito-nuclear communication)
