Week 5

Question 1

Mitochondrial Characteristics

Answer 1

1. 67% Matrix, 21% Inner Membrane, 6% O.M, 6% IMS
2. Circular dsDNA (16568 bp, 2 rRNA, 22 tRNA, 13 P)
3. Binary fission allows splitting ends to align along microtubules (PP interactions for transport and position
4. Semi-autonomous, no introns, 93% coding
5. Mt + Host: nuclear genes 70+ proteins of OxPhos and 1000+ other mt.Proteins for Rep/Trans/FA metab
6. Threshold of pheno. expression depends on E

Question 2

MtDNA Origins

Answer 2

1. Hot-spot for mutation: ROS in ETC, no histones, requires more replication, 93% coding (silent/patho)

Question 3

Genetic Bottleneck (mtDNA)

Answer 3

Fertilized zygote –> blastocyst with zona pellucida + implantation –> primordial germ cells –> mature
> 100000 mitochondria/oocyte: no replication x rounds of zygotic division –> 100000/2^x –> bottleneck
> Not prone to recombination

Question 4

MERRF (Rare)

Answer 4

1. Childhood onset, heteroplasmy
2. Transient seizure, poor coordination, few/poor muscle cells, and poor spinal curve (ragged red fiber stained in complex II of ETC)
3. P-mutation of tRNA lysine (MTTK*MERRF8344G)
   > 90% mt affected: nerve/muscle cell mt. protein synthesis decreased due to interfering linkage between tRNA and lysine/codon-codon interaction (A to G)

Question 5

MELAS (MOST COMMON MImt Disease)

Answer 5

1. Strokes, ataxia, myopathy, migraine
2. P-mutation of 1 Leu tRNA genes (MTTK*MELAS3243G) > 80% mt affected: Low pyruvate usage –> excess buildup become lactic acid –> low blood pH

Question 6

LHON (Rare)

Answer 6

1. 5x in MALES, homoplasmy
   2.Poor Eyesight
2. 18 different missense mutation in 9 mt genes
   > can be primary or multiple (in Complex I function of respiratory chain)

Question 7

Kearns-Sayes Syndrome

Answer 7

1. Sporadic SOMATIC 5 kb deletion

> heart, nerve/eye muscle problems: limited eye movement –> 100% immobility

Question 8

Mt Disease Treatment (no cure yet)

Answer 8

1. Vitamin, O2 radical scavengers. artificial e- acceptors to decrease ETC block
2. Pronuclear Transfer: malfunctioning mt in egg and normal sperm fertilized –> fertilized pronuclear placed in normal egg –> grows into embryo in uterus
3. Spindle Transfer: Spindle and mt Chomosomes placed in donor egg first –> fertilized with sperm –> embryo in uterus
   * *Controversies with mtDNA replacement: okay with boys because fathers do not pass on mt gene, so boys cannot pass on donor genes

Question 9

Bcl2 Family

Answer 9

1. Anti-apoptotic: BH4, 3, 1, 2
   > Without apop. signal –> Bcl2 binds to mt. membrane –> no BH123 release –> cell live
2. Pro-apoptotic: BH3, 1, 2 (Bax, Bak)
   > Apop. signal –> BH123 binds to mt. membrane –> cytochrome C release into cytosol –> DEATH
   > MICE WITHOUT BH123 is resistant to this
3. Pro-apoptotic: BH3 (Bim, Bad, Bid, Noxa, Puma)
   > Apop signal –> Bcl2 doesn’t bind to mt membrane –> BH123 release –> DEATH
   ** Cancer wants long cell life: so increase anti-apoptotic and decrease pro-apoptotic