Lecture 10: The Important of Mitochondria in Health and Disease Flashcards Preview

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Flashcards in Lecture 10: The Important of Mitochondria in Health and Disease Deck (20)
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How can ATP leave the mitochondria and ADP enter it?

A large outer membrane voltage-dependent anion channel called adenine nucleotide translocase.


How many charges do ATP and ADP have at physiological pH?

ATP has 4 negative charges and ADP has 3 negative charges.


What is ATP/ADP transport driven by?

Membrane potential (from movement of charged molecules)


How does Pi enter the mitochondria?

Phosphate (Pi) re-enters the mitochondrial matrix in an electro-neutral symport mechanism with H+. Pi transport is driven by, and uses up, the pH gradient.


How are molecules transported across the impermeable inner mitochondrial membrane?

Protein carriers. There are protein carriers in the inner mitochondrial membrane which are specific to every molecule which needs to be transported, e.g. pyruvate.


What is the function of the malate aspartate shuttle?

To transfer e- from cytosolic NADH to mitochondrial NAD+ to form mitochondrial NADH. This occurs through the reduction and regeneration of oxaloacetate and is responsible for the yield of just over 2 ATPs for every cytosolic NADH.

In the cytosol oxaloacetate is converted to malate with NADH as a cofactor. In the IMM there is a carrier protein which can transport malate, so malate can enter the matrix and be converted to oxaloacetate there, giving the e- to NAD+ to form mitochondrial NADH. The rest of the reactions are to regenerate oxaloacetate in the cytosol.


What is the influx of calcium into the mitochondrial matrix driven by?

Membrane potential (movement of charged ions).


What is the efflux of calcium into the mitochondrial matrix driven by?

Exchange from Na+


What happens when the Ca2+ concentration in the cytosol rises?

The rate of influx into the mitochondrial matrix increases and the rate of efflux stays constant, until the Ca2+ concentration has returned to the set point.


What prevent ROS from attacking macromolecules in our body?

Antioxidant enzymes


What is the first target of ROS?

Mitochondrial DNA


What does the mitochondrial DNA mostly code for?

Complex 1


What happens when ROS causes damage to the mitochondrial DNA?

The mitochondrial DNA mutates, causing the Complex 1 proteins produced to be defective. The ETC cannot continue. Complex 1 produces even more ROS. Cytochrome c detaches from the IMM and enters the cytosol, signalling apoptosis for the defective mitochondria.


What causes the most ROS?

Complex 1 and the quinone pool


Give two ways the cell uses ROS.

1) Immune cells uses ROS to kill pathogens
2) ROS signalling pathways exist in non-immune cells


When is a voltage-dependent anion channel open/closed?

A voltage-dependent anion channel is open at low or zero membrane potential and closed at potential above 30-40 mV.


How does the release of cytochrome c into the cytosol signal apoptosis?

Cytochrome c in the cytosol activates proteolytic enzymes called caspases, which play a major role in cell death.


What is Mitochondrial Permeability transition?

An increase in the permeability of the mitochondrial membranes during certain pathological conditions such as traumatic brain injury and stroke. It can lead to mitochondria swelling and cell death. The pressure of free radicals (result of excessive calcium concentrations) will open the pore, increasing the permeability.


What is autophagy?

Autophagy is the process of degrading cellular components by transporting them to the lysosome.


What is mitophagy?

Selective autophagy of mitochondria. Triggered by protein in outer mitochondrial membrane. Balancing process for mitochondrial turnover - maintains healthy mitochondrial population, removes defective mitochondria, prevents excessive production of ROS.