Mitochondria and Peroxisomes Flashcards
What is the function of peroxisomes?
They have important roles in cellular metabolism
Also medically important because of peroxisomal disorders
What is the Endosymbiotic Theory?
The theory proposes that all of the mitochondria can be traced back to one single prokaryotic cell
That prokaryotic cell, whilst engulfed by a eukaryotic cell, the two cells formed a symbiotic relationship
Some eukaryotes have lost mitochondria in evolution but retain a similar organelle e.g. mature red blood cells destroy their mitochondria
Describe the structure of the mitochondria.
Between the inner and puter membrane exists an inter-membrane space
Located within the inner membrane is the mitochondrial matrix
This is where a vast number of metabolic reactions take place
The large protein complexes responsible for oxidative phosphorylation are embedded in the inner mitochondrial membrane
The architecture of the mitochondria, the presence of two membranes, the presence of a small circular genome are clues that support the notion that mitochondria originate from a prokaryotic ancestor
How do mitochondria vary in different types of cells?
Mitochondria form networks and are organised differently depending on the cell type
In skin fibroblast cells they are interconnected, forming networks with one another
This network is also dynamic, the mitochondria are constantly moving in the cell, individual mitochondria separate from the network, they can divide and fuse (fission and fusion)
In cardiac cells, mitochondria are highly abundant and can be found to reside in distant zones
This raises the possibility that distinct subcellular populations of mitochondria, may perform zonal-specific functions necessary for cardiac myocyte function
How are mitochondria transported?
Mitochondria are transported on cytoskeletal microtubules
A process that requires the 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 neurones whereby mitochondria are channelled along axons and delivered to synapses where they are required for neuronal signalling and function
Recall the mitochondrial life cycle.
When there are new mitochondria made, they are not made from scratch, rather the process involves growing the mass of existing mitochondria, which then undergo fission
The process of fusion’s physiological role is less clear
Over time, macromolecules inside mitochondria such as DNA and proteins become damaged, typically as a result of oxidative insults
To maintain overall cellular health, these damaged mitochondria are eventually removed from the cell in the process of mitophagy
What are the functions of mitochondria?
Its main function is to produce ATP in the process of oxidative phosphorylation
However, they are also central hubs of metabolism in the cell e.g. they are also important for the anabolic synthesis of nucleotides acquired for DNA replication and growth
This is one reason why mitochondrial function has emerged as an important target for cancer therapy
In addition, mitochondria play a role in calcium homeostasis, critical for muscle contraction
Also important for the production of AAs such as glutamate, which have a function as neurotransmitters
Recently been found to have a role in immune responses
There are protein receptors that detect invading viral RNA molecules and are located on the outer membrane of the mitochondria
These activate an innate immune response
How is ATP generated through oxidative phosphorylation?
Nutrients in our food are oxidised to produce Acetyl CoA, which is processed in the citric acid cycle (TCA/Krebs cycle)
In the subsequent reactions in the TCA cycle, the molecules NADH and FADH are produced
These serve as electron donors in the electron transport chain and ultimately results in the production of ATP
What are the steps of the Citric Acid Cycle?
- Acetyl CoA (2C) reacts with Oxaloacetate (4C) to give Citrate (6C) catalysed by Citrate synthase
- Isomerisation of Citrate into Isocitrate by the enzyme Aconitse (Technically its Citrate to cis-Aconitase then to Isocitrate (both catalysed))
- Next Isocitrate is oxidised into alpha-ketoglutarate (5C) by the enzyme Isocitrate dehydrogenase
In this reaction, 1 molecule of NAD is reduced to NADH and 1 molecule of CO2 is produced - alpha-ketoglutarate is converted to succinyl-CoA (4C) by the enzyme alpha-ketoglutarate dehydrogenase
One molecule of NAD turns to NADH and 1 molecule of CO2 is produced
5.Succinyl-CoA is converted to Succinate (4C) by the enzyme succinyl CoA synthase
1 molecule of GTP is produced
6.Succinate is converted to Fumarate by the enzyme succinate dehydrogenase
1 molecule of FADH2 is produced
Succinate dehydrogenase is also involved in oxidative phosphorylation its found in the inner membrane of the mitochondria which is unlike all the other citric cycle enzymes which are soluble enzymes inside the mitochondrial matrix - Fumarate is converted into Malate by the enzyme Fumarase
- Malate is converted into Oxaloacetate (4C) by the enzyme Malate dehydrogenase
NAD is converted to NADH (1 molecule)
Where does Acetyl CoA come from to be used in the Citric Acid Cycle?
The Acetyl-CoA is derived from the metabolism of carbohydrates in the cytoplasm and from fatty acids metabolised by the process of beta-oxidation that takes place in the mitochondria
What are the two important functions of TCA?
To produce reduced electron donors NADH and FADH2
These are used for the production of ATP in oxidative phosphorylation
To provide biosynthesis precursors for the biosynthesis of fatty acids and amino acids
These two different functions represent two physiological states
The catabolic state where energy is released during the breakdown of molecules vs the anabolic state where energy is consumed in the synthesis of larger molecules
What are the stages of oxidative phosphorylation?
There are two key stages to it:
1.Generation of a proton motive force (electron transport chain/respiratory chain)
Electrons derived from NADH and FADH2 generated in TCA flow through the respiratory chain complexes
The flow of electrons leads to protons being pumped out of the matrix into the intermembrane space
The buildup of protons generates a proton motive force consisting of transmembrane potential and a pH gradient
2. Chemiosmosis (ATP synthase)
The protons are transported back into the matrix by a separate protein complex called ATP synthase drives the synthesis of ATP
This flow of protons through the ATP synthase drives the synthesis of ATP
What are the 5 protein complexes embedded in the inner mitochondrial membrane?
NADH dehydrogenase/ complex I
Succinate dehydrogenase/ complex II
The cytochrome BCI complex/ complex III
Cytochrome C oxidase/ complex IV
ATP synthase/ complex V
Complexes I-IV are involved in the transfer of electrons and generation of proton motive force hence these 4 complexes are part of the electron transport chain also known as the respiratory chain complexes
In addition, there are also two small electron carriers, Ubiquinone and Cytochrome C
Recall the process of OXPHOS (electron wise).
The molecules NADH and FADH2 generated in the TCA cycle donate electrons to the ETC
NADH electrons enter complex I -NADH –> NADP+
As complex I becomes charged with the electrons, protons are transported from the matrix side to the intermembrane space by the complex
The consequence of this is that a trans-membrane potential is generated whereby the intermembrane space is +vely charged relative to the -vely charged matrix
Electrons from FADH2 enter the ETC at complex II, in this reaction FADH2—>FAD
Complex II does not pump protons, therefore, doesn’t contribute to the proton motive force
Electrons from complex I or II are then transported to the electron carrier ubiquinone and then onto complex III
Electrons from complex III are transported to complex IV by the electron carrier cytochrome C
Both complex III and IV pump protons across the membrane
The final step of the ETC occurs at complex IV when the electron is donated to the terminal electron acceptor, oxygen, which is reduced to water
Due to the high buildup of protons in the intermembrane space, these protons then flow back into the matrix through complex V which harnesses the energy from the flow of protons to generate ATP
What are the functions of peroxisomes?
There are two main functions that take place inside peroxisomes:
Some fatty acids are broken down inside the peroxisomes in the process of beta-oxidation- also take place in the mitochondria but it is unable to break down the longer chains
The detoxification of the harmful molecule hydrogen peroxide
H2O2 is a reactive oxygen species that can react with and damage macromolecules such as DNA and proteins
This type of oxidative damage has been thought to cause cellular dysfunction and contribute to the ageing process
There are additional functions including the metabolism of bile acids which are important in digestion and the synthesis of cholesterol
