Mitochondria

Inner Membrane

ETC located on the inner mitochondrial membrane where H+ are pumped into the intermembrane space

Electrochemical concentration is created that will be used to create ATP

Outer membrane

Porin- allows for diffusion of small ions like Mg and water to pass through freely into intermembrane space.

Translocase of outer membrane: Controls passage of larger proteins into the mitochondria

Mitochondrial lipid synthesis occurs here

Means enzymes for fusion and fission are present

Matrix

Surround cristae and is filled w/ a gel like substance

Oxidation of pyruvate or small fatty acids to acetyl CoA occur here

Kreb's cycle occurs here.

Mitochondrial DNA reside here. Each one is composed of 2 circular strands

Machinery for mitochondrial gene expression are here

Mitochondrial ribosomes and tRNA.

Cardiolipid: four fatty acid chain that allows for conc. gradient due to its high impermeability. Makes majority of inner membrane

5 complexes of ETC

Complex 1

Takes e- off of NADH

Toxin: Rotenone

Inhibits complex 1

Complex 2

Takes off e- off of FADH

Ubiquinone- e- carrier of both complex 1 and 2

Complex 3

Both pump protons into intermembrane space

Takes e- from ubiquinone and continues pumping

Cytochrome C carries e- to Complex 4

Complex 4

Dumps e- into oxygen. Water byproduct is made here.

Inhibition of this complex only decreases efficiency of ETC

Complex 2 can still get e-

Oxygen must be taken in to dump the used up e-.

Toxin: Anti-mycin: inhibits complex 3

This blocks oxygen consumption bc it stops the ETC.

Toxins: CO, Azide, and Cyanide

Inhibits this complex

Blocks oxygen consumption and stops ETC

Due to H+ pumping from matrix to intermembrane, matrix has a negative potential. (Voltage gradient)

This contributes to chemiosmosis.

Complex 5: ATP synthase

Uses chemical and voltage gradient to move H+ back to matrix and use the energy from this to make ATP.

Toxin: Oligomycin

Loss of ATP production

Any loss of ATP production will increase fermentation

Increased fermentation results in lactic acid buildup. Lactic acidosis

Uncouplers

Produce heat via speeding up ETC through increased inner membrane permeability.

Decreases ATP efficiency but heat is produced.

Chemicals

Thermogenin (UPC1)

2,4 dinitrophenol (DNP)

Found in brown fat

Increased Oxygen consumption

Synthetic chemical; lethal at high doses.

ADP/ATP translocase moves the ATP and stuff in/out the matrix.

Inhibition prevents ATP synthesis

Energy used for many processes

ATP production

Pyruvate transport into matrix

Inorganic phosphate into matrix

Used for ADP/ATP translocase activity.

Toxins: ABC

Bongkrek acid

Atractyloside

carboxyatractyoloside

E- escape from ETC can react w/ oxygen and form harmful free radical superoxide (O2-)

Sites for escape: Complex 1 + 3; Ubiquinone

Manganese superoxide dismutase (Mn-SOD) in matrix converts the free radical to H2O2

Catalase or glutathione peroxidase can degrade it into water and oxygen.

H2O2 can also react again with free radical.

No histones and introns = susceptible to damage

Relaxed codon usage: no wobble used

Mutation often impair oxidative phosphorylation enzymes.

Mutation inheritance: Homoplasmy or Heteroplasmy

Homoplasmy: all mitochondrial genome are identical; still difficult to predict disease bc penetrance is variable

Disease: Hereditary optic neuropathy

Heteroplasmy: Presence of normal and mutated mtDNA; results in variable mitochondrial disease

Heteroplasmy threshold: Mutation is functionally recessive and phenotype won't show if there is sufficient expression from the normal mtDNA.

Ex. Genetic bottleneck: During selection of oocytes, a select number of mtDNA are selected. Could mean variance in disease phenotype as a result.

Ex of disease: Myoclonic epilepsy

Peroxisomes (microbodies)

Enzymes of peroxisome like catalase break down substrates in an oxidation rxn.

Very important in breakdown of very long-chain-FA.

Beta-oxidation provides acetyl CoA through the breakdown of those FA

Alpha-oxidation

Catabolism of FA acids, Amino acids, and ethanol

Cholesterol, bile acids, and plasmolagens(membrane phospholipid) synthesis.

Peroxisome biogenesis

Composed of peroxin proteins (PEX)

Imported via ATP-dep transporter

Plasmalogen required for myelin sheathes.

Peroxisomal disease

Disorders of peroxisome biogenesis i.e. lack of peroxisomes

Single peroxisomal enzyme deficiencies

Zellwegers syndrome: caused by mutation of one of PEX genes

S/Sx: Craniofacial abnormalities, neurological and liver dysfunction. Elevated FA in blood. Most severely affected die in the first year.

Refsum disease: Mutation in PHYH or PEX7 which are involved in alpha oxidation of phytanic acid

S/Sx: Vision and olfaction loss; bone abnormalities in hands/feet; progressive muscle weakness and atrophy

Phytanic acid comes from diet and must undergo alpha oxidation prior to beta oxidation. Build up neg affects myelin sheath growth and fx.