Transport In Mitochondria

- Most mitochondrial and all peroxisomal proteins are encoded by the nuclear genome

- Mitochondria has multiple membranes- this means there is a complex arrangement of proteins within the organelle

What do mitochondria do

Their primary function is energy production

Make large amounts of ATP

- First step is glycolysis- the breakdown of glucose to pyruvate, this occurs in the cytoplasm

- Pyruvate enters the mitochondria- CO₂ is removed from the pyruvate, the remainder of the molecule enters the TCA cycle

- 1' function to produce H+ gradient across the inner mitochondria membrane- this drives ATPase

- Has a key role in Apoptosis

Mitochondria structure

- Have a double membrane

- Outer membrane encloses the organelle

- The inner membrane is highly folded. The folds are called cristae

- The inner matrix contains the enzymes

***Outer membrane structure***

- Perforated with large channels (porins), these allow entry of molecules < 5000 kDa

- Contains enzymes involved in lipid synthesis

***Intermembranespace***

- Contains enzymes that use ATP to phosphorylate other nucleotides

- H+ is pumped into this spice to create the proton gradient which drives Oxygen phosphorylation

***Inner membrane**

- Folded into christae which maximises surface area

- Contains REDOX performing proteins of the electron transport chain

- Proteins for ATP synthesis

- Transports proteins to move molecules in and out of the matrix

***Matrix***

- An Internal space containing enzymes of the Krebs Cycle (involved in respiration)

- Contains

1. Mitochondrial DNA

2. Ribosomes

3. tRNAs

4. Enzymes (TCA, b-oxidation metabolites such as TCA urea cycle, Ca++, K+, Mg++)

Mitochondrial Genetics

Mitochondria contain their own genetic material

- Circular chromosome (double stranded)

- Approximately 15-17kpbs

- Encodes 37 genes

- Mitochondrial DNA is inherited from the mother

Mitochondrial life cycle: At any point in time, mitochondria are in a dynamic flux between fission and fusion which ends in mitophagy

How do proteins get into mitochondria

Proteins are fully synthesised and then are translocated into the mitochondria, also uses signal sequences

Uses translocation proteins embedded in the outer and inner mitochondria membrane

- TOM= translocator of the Outer Membrane

- SAM= sorting and Assembly Machinery

- TIM= translocator of the inner membrane

- OXA= cytochrome oxidase activity

How do proteins get into the mitochondrial matrix?

N-terminal signal sequence which is recognised by the TOM complex

The protein translocates through TOM and TIM23

Then translocates through TIM23 into the matrix

The signal is then cleaved off

***Mitochondrial Precursor Proteins are Imported as Unfolded Polypeptide Chains***

Important to remember that proteins are fully synthesised before translocating into the mitochondria

To stop proteins from folding before docking with the TOM complex

- You bind interacting proteins to the newly synthesised polypeptide chain (eg: chaperones)

- Proteins are then imported into mitochondria unfolded

Chaperones need energy (ATP) to dissociate from the polypeptide chain

The signal sequence is +ve charged

The electrochemical H+ gradient driven by electron transport has two effects

1. ATP production

2. Membrane potential drives the +ve charged signal sequence through the IMM (Inner membrane)

Getting proteins into mitochondrial outer membrane

- Major proteins in OMM are called porins

- They are beta-barrel proteins

- A problem is that TOM cannot insert proteins into bilayers

- The solution to this is to keep proteins in the inter membrane space, unfolded by chaperones

Getting proteins into mitochondrial inner membrane and inter membrane space is varied

Most common route= using the inner mitochondrial membrane: uses TOM and TIM23

2nd route=

- Protein enters matrix space

- Signal sequence cleavage unmasks a 2nd signal that results in insertion into OXA complex

(OXA is the same complex that inserts mitochondrially translated proteins)

***Multipass IMM proteins=***

Move through TOM as a loop

This allows binding of chaperones which stopes folding and guides towards TIM22

**Peroxisomes

- Contain a variety of oxidative enzymes- eg: catalase and urate oxidase

- Function to remove hydrogen atoms from various organic compounds according to the reaction

RH2 + O2--- R + H2O2

This peroxide is used by peroxidases in other reactions

H2O2 + R’H2 --- R’ + 2H2O

In the liver, peroxisomes have a role in detoxification- 25% of alcohol is converted in this pathway