eukaryotic cell organelles
TRANSCRIPT
Eukaryotic cell organelles
http://www.jeffdonofrio.net/DNA/DNA_Analysis.html
Inheritance• Each cell has MANY mitochondria
• Oocytes have many mitochondria
• Sperm mitochondria are specialized, jettisoned at fertilization
• Mitochondria are only MATERNALLY inherited
Mitochondrial Function• Energy production- via Krebs Cycle ATP
• Glucose pyruvate = 2 ATP
• Pyruvate CO2 and H20 = 34-36 ATP
• Calcium homeostasis
• Role in apoptosis
• Role in blood and hormone synthesis
• Main tissues with high energy needs• Brain, heart, liver, muscles, respiratory,
endocrine
Human mitochondrial genome
Nageswara R. Madamanchi, and Marschall S. Runge Circulation Research. 2007;100:460-473
Copyright © American Heart Association, Inc. All rights reserved.
37 genes ~17,000 bp• 13 polypeptides, • 22 tRNAs,• 2 rRNAs).
Mitochondrial Dysfunction• Loss of motor control
• Muscle weakness
• Seizures
• Visual and auditory problems
• Poor growth
• Cardiac disease
• Liver disease
• Developmental delays
• Susceptibility to Infection
Variants in mitochondrial genes variety of diseases• 1 in 200-250 live births has a potentially
pathogenic mitochondrial DNA mutation Often
• delayed onset• Not directly lethal
• 45 listed on site- United Mitochondrial Disease Foundation diseases of mitochondrial function -www.umdf.org
Could Replacement of Mom’s Mitochondria Repair the Problem?
During Female embryonic
development
After pubertyAt each cycle
Overview of spindle-chromosomal complex transfer
Videomms://media.ohsu.edu/host/hosp/replacement.wmv
Healthy Baby
IVF required for embryo development
(Photo Credit: Mr. J. Conaghan)
http://stemcells.nih.gov/info
Placenta Embryo
Mitochondria appear everywhere except near the chromosomes
Visualization of the spindle during enucleation avoids damage
Spindle-chromosomal complex successfully isolated
Karyoplast contains ~1.5% volume compared to a cytoplast
Karyoplast inserted into perivitelline space
Karyoblast with patient’s spindle
Fusion using Sendai virus extract yields metaphase II chromosomes
Movie
mms://media.ohsu.edu/host/hosp/replacement.wmv
Chronology of innovation• Late 1990s: Cytoplasmic transfer leads to ~100 births
worldwide• 2001: FDA halts cytoplasmic transfer• September 2009: Mitochondrial gene replacement in
primate offspring and embryonic stem cells• May 2010: Pronuclear transfer in non-viable human
embryos• October 2012: Mitochondrial gene replacement in
human embryos to blastocyst stage• January 2013: Two additional studies demonstrating
feasibility in human
Success rate: 4 healthy births
Mito and Tracker
15 spindle-transfer embryos implanted into
9 recipients
Sequencing confirms mixed parentage
Pronuclear transfer is an alternate approach
Some mitochondria may also be transferred