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Acknowledgements

A very special thanks to


Dr. Amy Siegesmund, Topic Mentor
My Capstone Peers
All of my Biology Professors

Mitochondria: Power house of the cell

The Electron Transport Chain Perez-Acin, et al. 2007

Mitochondrial Disease
Any disease involving the electron
transport chain
Early vs late-onset

www.umdf.org (http://www.umdf.org/site/c.8qKOJ0MvF7LUG/b.7929671/k.BDF0/Home.htm )
Xander Brooks, Courtesy of Dr. Shane O.P. Brooks, D.O. (father)

MD results from direct and indirect


effects of complex formation
Direct Effects
Mutations in nDNA lead to improper protein folding and
subsequently complex malfunction
Supercomplexes form in the mitochondria

Indirect Effects
Mutations in accessory proteins leads to malfunction of the
complexes, secondary to the loss of function of the
supporting proteins
severe mtDNA mutations produce non-viable offspring,
leading to an early termination of pregnancy

Mutations in nDNA lead to improper protein folding


and subsequently complex malfunction
Saada, et al. 2007

NDUFS3 inhibited by Chloramphenicol. GFP-tagged NDUFAF3 shows an increase in


intermediates (indicated by arrows) and a decrease in IGA. (Saada, et al. 2007)

Subcomplex Formation

Saada, et al. 2007

MD results from indirect and direct


effects of complex formation
Direct Effects
Mutations in nDNA lead to improper protein folding
and subsequently complex malfunction
Supercomplexes form in the mitochondria

Indirect Effects
Mutations in accessory proteins leads to
malfunction of the complexes, secondary to the
loss of function of the supporting proteins

Mutations in accessory proteins leads to


malfunction of the complexes
Thymidine Kinase 2 (TK-2) is a common accessory protein
Decrease mtDNA caused a 20-30% decrease in CI, III, and
IV activity. 25% reduction in CI and CIII dependent activities

Mitchondrial Respiratory Chain Activities in Patients with TK-2 Mutation

Gtz A et al. Brain2008;131:2841-2850

MD results from indirect and direct


effects of complex formation
Direct Effects
Mutations in nDNA lead to improper protein folding
and subsequently complex malfunction
Supercomplexes form in the mitochondria

Indirect Effects
Mutations in accessory proteins leads to
malfunction of the complexes, secondary to the
loss of function of the supporting proteins

Supercomplexes form in the


mitochondria
Calvaruso, et al. 2012

Calvaruso, et al. 2012

MD results from indirect and direct


effects of complex formation
Direct Effects
Mutations in nDNA lead to improper protein folding
and subsequently complex malfunction
Supercomplexes form in the mitochondria

Indirect Effects
Mutations in accessory proteins leads to
malfunction of the complexes, secondary to the
loss of function of the supporting proteins

Conclusion/Future Implications
Mutations in nDNA and mtDNA lead to
poor complex formation

Complex malformation leads to poor


electron transport and energy production

Xander Brooks, Courtesy of Dr. Shane O.P. Brooks, D.O. (father)

http://mitochondrialdiseases.org/related-diseases/

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