W3 Mitochondria + peroxisomes

Question 1

Three person baby

Answer 1

Mothers egg w/unhealthy MC has it’s nucleus removed
Donors nucleus removed and destroyed
Mothers nucleus now in donor egg

Question 2

Structure of MC

Answer 2

Double membrane
Outer membrane 
Inner membrane space
Inner membrane
Cristae w/folds = high SA
Cristae junctions = tubular structures + allow selective concentration of enzymes + important for inter-mitochondrial communication as cristae of nearby mitochondria arrange themselves to be parallel to each other and perpendicular to the connections between mitochondria
Associated w/microtubules
Has plasticity
1-2 um lenght
0.1-0.5 um width

Question 3

When does mitochondria morphology (shape) change?

Answer 3

Apoptosis (programmed cell death)
Ca2+ transfer
Cell cycle
Nutrient starvation

Question 4

Starvation induces mitochondrial tubulation

Answer 4

MEFs (mouse embryonic fibroblasts) were transfected with mito-YFP (yellow fluorescent protein).
(Upper) Cells were starved 16 h after transfection (introducing naked or purified nucleic acids for 2 h, and live images were acquired. (Images in the second row are magnified views of the boxed areas in first row.)
(Lower) Mitochondrial morphology was scored as follows: fragmented, mainly small and round; intermediate, mixture of round and shorter tubulated; and tubulated, long and higher interconnectivity.

Question 5

Mitochondrial protein synthesis

Answer 5

Mitochondria contain DNA + that DNA encodes a gene, vast majority of proteins in MC encoded by genes that sit in nucleus (In cytosol RNA to precursor protein to imported protein in MC)

Question 6

Mitochondrial DNA

Answer 6

Mitochondrial chromosomes are circular, as in bacteria
Mitochondrial genes are inherited cytoplasmically from the mother
The mitochondrial DNA (‘mtDNA’) is located in the matrix
Mitochondria also contain their own ribosomes
Human mtDNA contains 16,569 base pairs that encode 2 rRNAs, 22 tRNAs and 50 proteins
Other mitochondrial proteins are encoded in the nucleus, translated in the cytoplasm and imported into mitochondria
The mitochondrial genetic code differs from the standard nuclear code. For example UGA is a stop codon in the nucleus but codes for tryptophan in mitochondria; conversely AGA and AGG usually code for arginine but are stop codons in the mitochondrial translation system

Question 7

MC functions

Answer 7

Breakdown of fatty acids to acetyl CoA
Decarboxylation of pyruvate to acetyl CoA
Citric acid cycle = pivotal metabolic pathway generating reducing equivalents for ATP generation and metabolic intermediates for anabolic pathways
Oxidative phosphorylation&raquo_space; formation of ATP and water from ADP, Pi, reducing equivalents and O2
Thermogenesis = generation of heat
Mitochondria play an important role during apoptosis (programmed cell death)

Question 8

MC ATP-generation

Answer 8

Outer membrane → protein pores for passage of ions + small proteins
Inner membrane → more restricted permeability, has proteins for e- transport + ATP synthesis. Surrounds mitochondrial matrix where kreb cycle releases e- which travel from one protein to next in inner membrane
Final e- acceptor is oxygen which forms water, e- transport chain produces ATP

Question 9

Localisation of MC where high levels of ATP required

Answer 9

Mitochondria arranged between muscle fibres + wrapped around flagellar axoneme (propels cell through liquid medium

Question 10

Beriberi

Answer 10

A neurologic and cardiovascular disorder, is caused by a dietary deficiency of thiamine (also called vitamin B1)

Thiamine pyrophosphate (cofactor) is a prosthetic group required for two mitochondrial enzymes, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase

Patients suffering from beriberi have higher than normal serum levels of these enzymes’ substrates (pyruvate and α-ketoglutarate)

Damage to the peripheral nervous system
Pain in the limbs
Weakness of the musculature
Distorted skin sensation
The heart may be enlarged and the cardiac output inadequate because muscle cells can’t generate ATP

Question 11

Peroxisome structure

Answer 11

Approximately 0.2 to 1 µm in diameter
Peroxisomes are surrounded by a single membrane
Contain no DNA or ribosomes
Most peroxisomal proteins are encoded in the nucleus, translated in the cytoplasm and then imported
At least some peroxisomal membrane proteins originate in the ER

Question 12

Peroxisome function

Answer 12

All peroxisomes contain enzymes that use molecular oxygen to oxidize various substrates
Reactions produce hydrogen peroxide (H2O2), which is broken down to water by the enzyme catalase (one of the most abundant in peroxisomes)
Peroxisomes are important for the metabolism of long-chain fatty acids (standard fatty acid chains broken down in mitochondria)
Peroxisomes perform critical steps in the synthesis of certain lipids, e.g. cholesterol, plasmalogens (specific membrane lipid - glycerophospholipids) + bile acids
Breakdown of excess purines (components of nucleotides like AMP, GMP) to uric acid
Crystalline core = highly rich in enzymes, the [] is so high that these proteins form crystals

Question 13

Peroxisome biogenesis

Answer 13

Precursor vesicles that pinch off from the endoplasmic reticulum
Nearly all soluble proteins in lumen of peroxisome synthesised in cytoplasm

Growth by uptake of speficic peroxisomal proteins and lipids from cytosol then daughter cells formed by fission

Peroxisome diseases mainly due to problems with import of those proteins made in cytoplasm