AcknowledgementsA very special thanks toDr. Amy Siegesmund, Topic MentorMy Capstone PeersAll of my Biology Professors

Mitochondria: Power house of the cellThe Electron Transport Chain Perez-Acin, et al. 2007

Mitochondrial DiseaseAny disease involving the electron transport chainEarly vs late-onsetXander Brooks, Courtesy of Dr. Shane O.P. Brooks, D.O. (father)www.umdf.org (http://www.umdf.org/site/c.8qKOJ0MvF7LUG/b.7929671/k.BDF0/Home.htm )

MD results from direct and indirect effects of complex formationDirect EffectsMutations in nDNA lead to improper protein folding and subsequently complex malfunction Supercomplexes form in the mitochondria

Indirect EffectsMutations 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 malfunctionNDUFS3 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. 2007Saada, et al. 2007

MD results from indirect and direct effects of complex formationDirect EffectsMutations in nDNA lead to improper protein folding and subsequently complex malfunction Supercomplexes form in the mitochondria

Indirect EffectsMutations 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 complexesThymidine Kinase 2 (TK-2) is a common accessory proteinDecrease mtDNA caused a 20-30% decrease in CI, III, and IV activity. 25% reduction in CI and CIII dependent activitiesMitchondrial 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 formationDirect EffectsMutations in nDNA lead to improper protein folding and subsequently complex malfunction Supercomplexes form in the mitochondria

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

Supercomplexes form in the mitochondriaCalvaruso, et al. 2012Calvaruso, et al. 2012

MD results from indirect and direct effects of complex formationDirect EffectsMutations in nDNA lead to improper protein folding and subsequently complex malfunction Supercomplexes form in the mitochondria

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

Conclusion/Future ImplicationsXander Brooks, Courtesy of Dr. Shane O.P. Brooks, D.O. (father)

Mutations in nDNA and mtDNA lead to poor complex formation

Complex malformation leads to poor electron transport and energy production

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