Mitochondrial Genetics

Mitochondrial Genetics

• several copies of ______ DNA molecule

• mitochondrial DNA (mtDNA) encodes ____% of the mitochondrial proteins

• all mitochondrial proteins are involved either in ______ or ______ ______

• nuclear DNA (nDNA) encodes ____% of mitochondrial proteins

• circular

• 5

• ETC, oxidative phosphorylation

• 95

Mitochondrial Genome

• circular DNA: ______ bp

• two strands: ______ & ______ strand

• the genome encodes ____ genes —> ____ tRNA, ____ rRNA, & ____ protein-coding genes

• 16,500

• heavy, light

• 37, 22, 2, 13

Which strand is guanine/purine rich?

H-strand

H-strand D-loop region has replication origin site

• ______ loop (D-loop) region contains:

  • 2 ______ ______ sites/heavy strand promoters —> ______

  • light strand promoter —> ______

  • replication origin of heavy strand —> ______

• displacement

• transcription initiation, HSP 1 & 2

• LSP

• OH

L-strand has its own replication origin site (OL)

• OL is located approximately ______ kb away from OH

• synthesized in the ______ direction of H-strand synthesis

• 11

• opposite

Mitochondrial Genome Replication is ______

• initiated at ____ different times from ____ different origins of replication

• ______ replication is initiated first

• ______ replication is initiated only after completion of ______ of the ______ replication

• the H-strand remains ______-stranded until L-strand replication is initiated

• asymmetric

• 2, 2

• H-strand

• L-strand, 2/3, H-strand

• single

Mitochondria are the major source of ______

• ROS are produced from the leakage of ____ to form superoxide ____ at complex I and complex III.

• produced as ______ during mitochondrial electron transport

• causes ______ & ______ damage

• reactive oxygen species (ROS)

• e-, O2-

• byproducts

• DNA, mitochondrial

mutation rate: ______ DNA > ______ DNA

• ______ proximity to ETC —> ______ chance of ROS-induced mitochondrial DNA damage

• no ______ proteins

• lack of DNA ______ ______

• mitochondrial, nuclear

• close, higher

• structural

• repair machinery

T or F:

Mitochondrial disorder can affect every organ in our body.

True

Mitochondrial disorder always follows ______ (maternal/paternal) inheritance.

maternal

Causes of Maternal Inheritance

1. ______ model —> sperms have very ______ (high/low) # of mtDNA 

   • sperm —> 100 copies. egg —> 100,000 copies.

2. ______ ______ model —> sperm’s mtDNA is ______, either before or after fertilization

• dilution, low

• active degradation, degraded

Types Based of mtDNA:

• ______ ______ —> identical and wild-type

• ______ ______ —> identical but mutant

• ______ —> existence of wild-type and mutant mtDNA —> variability in drug response may occur due to differing levels of functional mitochondria

• homoplasmic wild-type

• homoplasmic mutants

• heteroplasmic

Mitochondrial Threshold Effects

• ______ and ______ mtDNA coexist in the same cell

• ______ mtDNA will only cause symptoms when the # of copies exceeds a critical threshold

  • vary from mutation to mutation, organ to organ, and between different family members

• mutated, normal

• mutated

heteroplasmic mother may give birth to a normal child

• mutation > threshold —> ______ ______

• mutation = threshold —> ______ ______

• mutation < threshold —> ______ or ______

• highly symptomatic

• moderately symptomatic

• asymptomatic, normal

Drug-Induced Mitochondrial Toxicity

• certain drugs can impair mitochondrial function (3) —>

• tissues with ______ (high/low) energy demand are particularly vulnerable —> brain & muscle

• antiretrovirals, statins, chemotherapy agents

• high

Leber Optic Hereditary Neuropathy (LOHN)

• ______ form of vision loss

• results from the death of cells in the ______ ______ —> which transfers visual information from the ______ to the brain

• ______ ______ _____ (RGCs) process visual information

• treatment: ______, administration of the ______ analog, ______ and _______ supplementation

• inherited

• optic nerve, retina

• retinal ganglion cells

• Raxone, quinone, vitamin B12, C

Mitochondrial genome is transcribed as long polycistronic transcripts

• ______ mRNA —> mRNA that encodes only one protein —> eukaryotes

• ______ mRNA —> mRNA that encodes several proteins —> bacteria, mitochondria

• monocistronic

• polycistronic