mitochondria and peroxisomes

Question 1

what is the theory that explains the origin of mitochondria

Answer 1

• Endosymbiotic theory proposes that all mitochondria that has ever existed can be traced back to one single prokaryotic cell.
• Prokaryote was engulfed by primitive form of eukaryotic cell. The two cells subsequently formed a symbiotic relationship. The prokaryote divided inside the host, producing daughter cells, and increasing their number so that when the host cell divided the prokaryotic daughter cells were passed on.
• This host cell gave rise to all known eukaryotic organisms that have ever lived- evidence – phylogenetic
• Some eukaryotes have lost mitochondria in evolution but retain a similar organelle.

Question 2

give an example of a cell that destroys its mitochondria

Answer 2

red blood cell

Question 3

describe the organisation of mitochondria in fibroblast cells.

Answer 3

they are interconnected forming networks of one another. This network is highly dynamic, with the mitochondria constantly moving in the cell.

• Individual mitochondria can separate from the network, they can divide and they can fuse with other mitochondria in a process called fission and fusion.

Question 4

describe the organisation of mitochondria in cardiac cells.

Answer 4

• In cardiac cells, mitochondria are highly abundant.
• They are found to reside in distinct zones – possibility that distinct subcellular populations of mitochondria may perform zonal specific functions necessary for cardiomyocyte function.

Question 5

How are mitchondria transported?

Answer 5

Mitochondria are transported on cytoskeletal microtubules.
• It’s a process that requires motor proteins dynein and kinesin, to which mitochondria binds by the adaptor proteins Milton and Miro which are located on the surface of mitochondria.

• Transport of mitochondria is important in cells such as neurons whereby mitochondria are channelled along axons and delivered to synapses where they are required for neuronal signalling and function

Question 6

describe the structure/architecture of mitochondria

Answer 6

• Consists of double membrane, known as the inner and outer membranes
• between the inner and outer membrane is the intermembrane space.
• Located within the inner membrane is the mitochondrial matrix. This is where the vast number of metabolic reactions take place.
• The large protein complexes that are responsible for process of oxidative phosphorylation are embedded in the inner mitochondrial membrane.
- small circular genome
• Cristae form from inner membrane folding to increase surface area (invaginated)

Question 7

what supports the notion that mitochondria originate from a prokaryotic ancestor

Answer 7

mitochondria have their own DNA

Question 8

how does the way mitochondria behave in cells reflective of their prokaryotic origin ?

Answer 8

. Like bacteria mitochondria can divide and fuse with another in a process known as fission and fusion.

Question 9

outline the mitochondrial life cycle

Answer 9

• When a new mitochondria is made, theyre not made from scratch, but rather the process of increasing mitochondria involves growing the mass of existing mitochondria which are then able to undergo fission.
• Overtime macromolecules inside the mitochondria such as DNA and proteins become damaged, typically because of oxidative insults
• To maintain overall cellular health, the damaged mitochondria are removed from the cell via mitophagy, a form of autophagy.

Question 10

what are the functions of mitochondria ?

Answer 10

• Produce ATP in the process of oxidative phosphorylation.
• Mitochondria are central hubs of metabolism within the cell, not just energy metabolism.
• They are important for the anabolic synthesis of nucleotides, which are required for dna replication and growth. Therefore mitochondria function has been emerged as an important target for cancer therapy.
• Play in role in calcium homeostasis. Important for muscle contraction
• Important for production of amino acids such as glutamate which are neurotransmitters.
• Important in apoptosis
• Involved in immune response. There are protein receptors that detect invading viral rna molecules. These protein receptors are located on the outer membrane of mitochondria. This activates an innate immune response.
• Breakdown of fatty acids to acetyl CoA.
• Decarboxylation of pyruvate to acetyl CoA (glycolysis)

Question 11

describe mitochondrial DNA

Answer 11

• Mitochondrial proteins can be produced from imported precursor or organelle DNA.
• Mitochondrial DNA is circular
• Located in the matrix
• Contain own ribosomes
• Mitochondrial genetic code differs from standard nuclear code. AGA is usually codes for arginine but are stop codons in mitochondria.

Question 12

how is ATP generated

Answer 12

oxidative phosphorylation

Question 13

what forms acetyl coenzyme A

Answer 13

• The acetyl-coA is derived from the metabolism of carbohydrates in the cytoplasm and fatty acids metabolised by beta oxidation that takes place inside the mitochondria.

Question 14

which 2 molecules are produced in the citric cycle that serve as electron donors in the etc

Answer 14

NADH and FADH2.

These electron donors are oxidised by the electron transport chain and result in the production of ATP.

Question 15

acetly-coA is completely oxidised to form what in the citric acid cycle ?

Answer 15

C02

Question 16

Where does the citric acid cycle take place ?

Answer 16

inside the mitochondrial matrix.

Question 17

how is citrate synthesised

Answer 17

combining acetyl-coA and oxaloacetate.

Question 18

outline the steps and reactions in the citric acid cycle .

Answer 18

1) Acetyl-CoA ( 2C) combines with oxaloacetate (4C) which forms citrate (6c). this reaction is catalysed by citrate synthase.
2) Isomerisation of citrate into isocitrate by the enzyme aconitase. This is a 2 step reaction that generates the intermediate cis-Aconitase.
3) Isocitrate is oxidised into alpha-ketoglutarate (5C) by the enzyme Isocitrate dehydrogenase. In this reaction one molecule of NAH is reduced to NADH and one molecule of C02 is produced.
4) Alpha-ketoglutarate is converted to succinyl-CoA (4C) by the enzyme alpha-ketoglutarate dehydrogenase. One molecule of NAH is reduced to NADH and another molecule of c02 is produced. – why its now 4c.
5) Succinyl-coA is converted to succinate by the enzyme Succinyl CoA synthetase. GTP is produced.
6) Succinate is then converted into fumarate by the enzyme succinate dehydrogenase. A molecule of FADH2 is produced. Succinate dehydrogenase is involved in oxidative phosphorylation. This enzyme is found in the inner membrane of the mitochondria, unlike other citric acid cycle enzymes which are soluble enzymes inside the mitochondrial matrix.
7) Fumarate is converted into malate by fumarase.
8) Malate is converted into oxaloacetate by malate dehydrogenase. NAH is reduced to produce an NADH.

Question 19

What are the products generated for one molecule of Acetyl-coA metabolised in the citric acid cycle ?

Answer 19

3X NADH
1X FADH2
2X C02
1X GTP

Question 20

What are the important functions of the citric acid cycle ?

Answer 20

• Reduce electron donors, NADH and FADH2, which are used for the production of atp in oxidative phosphorylation.
• Provide biosynthetic precursors for the biosynthesis of fatty acids and amino acids
• These two functions represent different physiological states : the catabolic state where energy is released during the breakdown of molecules, and the anabolic state, where energy is consumed in the synthesis of larger molecules.

Question 21

the flow of electrons leads to the protons being pumped from where to where? what does this generate.

Answer 21

The flow of electrons lead to the protons being pumped out of the matrix into the intermembrane space

. The build up of protons in the intermembrane space generates a proton motive force, consisting of a transmembrane potential and a PH gradient.

Question 22

what are the 2 key steps in oxidative phosphorylation

Answer 22

1) Electrons that are derived from NADH and FADH2, flow through the respiratory chain complexes. The flow of electrons lead to the protons being pumped out of the matrix into the intermembrane space. The build up of protons in the intermembrane space generates a proton motive force, consisting of a transmembrane potential and a PH gradient.
2) The protons are transported back into the matrix by atp synthase in a process called chemiosmosis. This flow of protons through the ATP synthases drives the synthesis of ATP.

Question 23

describe the proteins involved in oxidative phosphorylation

Answer 23

• Oxidative phosphorylation involves 5 protein complexes embedded in the inner mitochondrial membrane : NADH dehydrogenase – complex 1 , succinate dehydrogenase – complex 2, cytochrome BC1 complex – complex 3, cytochrome c oxidase – complex 4, and ATP synthase – complex 5.
• Complexes 1-4 are involved in the transfer of electrons and generation of proton motive force, and hence are part of the electron transport chain and are called the respiratory chain complexes.
• ATP synthases , the 5th complex, is not involved in electron transfer and therefore is not a respiratory chain complex.

Question 24

what are the 2 electron carriers in oxidative phosphorylation

Answer 24

ubiquinone and cytochrome c.

Question 25

outline the steps of oxidative phosphorylation

Answer 25

• Electrons from NADH enter complex 1. NADH is converted to NAP+ and donates electrons to complex 1
• As complex 1 becomes charged with the electrons, protons are transported by the complex from the matrix side to the intermembrane space. This generates a transmembrane potential, where the intermembrane space is positively charged, relative to the negatively charged matrix.
• Electrons from FADH2 enter complex 2.in this reaction FADH2 is converted into FAD. Complex 2 does not pump protons and therefore does not contribute to the proton motive force.
• Electrons form complex 1 or 2 are then transported to the electron carrier ubiquinone and then onto complex 3.
• Electrons from complex 3 are transported to complex 4 via the elctron carrier cytochrome C.
• Both complex 3 and complex 4 pump protons across the membrane and therefore contribute to the proton motive force.
• The final step of the etc occurs at complex 4, when the electron is donated to the terminal electron acceptor oxygen which is reduced to water.
• There is a high membrane potential resulting from the build up of positively charged protons in the intermembrane space. The proton then flow back into the matrix through complex 5 which harnesses the energy from the flow of protons to generate ATP by the phosphorylation of ADP with an inorganic phosphate.

Question 26

what are the products of oxidative phosphorylation

Answer 26

• 1x NADH = 2.5 x ATP

- 1x FADH2 = 1.5 x atp

Question 27

describe the structure of peroxisomes

Answer 27

• They have a single membrane bilayer
• Do not contain their own dna or ribosomes.
• Crystaillin core due to high concentration of proteins.

Question 28

what are the functions of peroxisomes ?

Answer 28

some fatty acids are broken down in the process of beta oxidation ( beta oxidation also takes place inside the mitochondria but mitochondira is unable to break down very long chain fatty acids)
• Long chain fatty acids are taken up and metabolised inside the peroxisomes
• The second function is the detoxification of the harmful molecules hydrogen peroxide by catylase.
• Hydrogen peroxide is a reactive oxygen species that can react and damage macromolecules like DNA and proteins. This form of oxidative damage has been thought to cause cellular disfunction and contribute to the aging process.
• There are additional functions of peroxisomes, including the metabolism of bile acids ( important in digestion and synthesis of cholesterol ).

-breakdown of purines

Question 29

which enzyme is responsible for detoxifying hydrogen peroxide and where is it located

Answer 29

• The enzyme that detoxifies hydrogen peroxide – catylase.- abundant in peroxisome and not elsewhere in the cell

Question 30

just like mitochondria, peroxisomes replicate by?

Answer 30

peroxisomal fission

Question 31

what are some proteins that are involved in the fission of both mitochondria and peroxisomes ?

Answer 31

DNM1L, FIS1

Question 32

describe shared features of mitochondria and peroxisomes

Answer 32

• Both important in cellular metabolism, eg. Metabolism of fatty acids
• Both are able to divide, and the protein machinery are located on the outside of both organelles.
• Antiviral signalling is a function shared by both organelles. The mitochondrial anti viral signalling complex – MAVs is found on the outermembrane of mitochondria and also on the membrane of peroxisomes.

Question 33

which organelle is important for cellular metabolism ?

Answer 33

peroxisomes