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4th Int. Conf. on Metabolomics & Systems Biology

Join us at the 4th International Conference on Metabolomics & Systems Biology to explore the functions of mitochondrial metabolism in cell proliferation and epigenetics. Learn about the latest research in this field and network with experts in Philadelphia, USA.

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4th Int. Conf. on Metabolomics & Systems Biology

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  1. AboutOMICSGroup OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 500 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS International also organizes 500International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions.

  2. AboutOMICSGroup AboutOMICSInternational Conferences OMICS International is a pioneer and leading science event organizer, which publishes around 500 open access journals and conducts over 300 Medical, Clinical, Engineering, Life Sciences, Pharma scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS International has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

  3. Dissecting the distinct functions of mitochondria 4th International Conference and Exhibition on Metabolomics & Systems Biology April 29, 2015 – Philadelphia, USA Inmaculada Martinez-Reyes – Dr. Navdeep Chandel Lab – Northwestern University, Chicago

  4. Mitochondrial metabolism is necessary for tumorigenesis.

  5. Mitochondria as signaling organelles. Glucose Pyruvate AMP/ATP Catabolism AMPK Acetyl-CoA ATP-Citrate Lyase Ac OAA IV II Citrate Acetyl-CoA V III I HAT Me TCA Cycle α-KG α-KG H2O2 H+ ADP NAD+ ATP JMJD3 NADH FAD e- FADH2 O2 H2O e- Q e- HIF NFkB ? H+ e- e- e- Q c Q c H+ H+

  6. What functions of mitochondrial metabolism are necessary for cell proliferation and epigenetics?

  7. Two functions of mitochondria: TCA cycle metabolites and membrane potential. H+ ETC NADH/FADH2 O2 H2O H+ TCA ADP ATP NAD+/FAD H+ Metabolites (Acetyl-CoA, Succinyl-CoA) Y (ATP, ROS, Iron-sulfur clusters)

  8. DNA polymerase gamma (POLG) is necessary for mitochondrial DNA (mtDNA) replication. Dominant Negative (DN-POLG) Doxycycline Doxycycline Dominant Negative (DN-POLG) Doxycycline (DOX) Hans Spelbrink

  9. Dominant negative POLG depletes mtDNA encoded RNA transcripts. WT PLOG + DOX Day 9 DN PLOG + DOX Day 0 Day 3 Day 6 Day 9 Ty Wang Janine Santos

  10. Dominant negative POLG depletes mtDNA encoded proteins. WT-POLG DN-POLG Days 0 3 6 9 0 3 6 9 Days 0 3 6 9 0 3 6 9 - - - - + + + + DOX - - - - + + + + DOX COXII COXII SDHA SDHA Tubulin Tubulin

  11. Loss of mitochondrial DNA does not induce cell death.

  12. Loss of mitochondrial DNA decreases oxygen consumption rate (OCR).

  13. Loss of mitochondrial DNA decreases mitochondrial membrane potential.

  14. Loss of mitochondrial DNA increases glucose catabolism. Biolog

  15. Loss of mitochondrial DNA induces dependence on glycolysis for survival.

  16. Loss of mitochondrial DNA induces AMPK activation. DN-POLG Days 0 0 3 3 6 6 9 9 - - + + + + + + DOX p-AMPK AMPK Tubulin

  17. Loss of mitochondrial DNA diminishes cell proliferation rate.

  18. Quantification of Histone modifications using Silac. He Huang Minimal changes in methylation and acetylation of H2B and H4. Yingming Zhao

  19. Loss of mitochondrial DNA decreases specific histone H3 acetylation. DN-POLG Days 0 3 6 9 - + + + DOX H3K9ac H3K14ac H3K18ac H3K27ac H3 total

  20. Mitochondria metabolism is necessary for cell proliferation and specific histone acetylation.

  21. Two functions of mitochondria: TCA cycle metabolites and membrane potential. H+ ETC NADH/FADH2 O2 H2O H+ TCA ADP ATP NAD+/FAD H+ Metabolites (Acetyl-CoA, Succinyl-CoA) Y (ATP, ROS, Iron-sulfur clusters)

  22. Electron transport chain couples electron flux to proton pumping. H+ H+ H+ Cyt c C-IV Q C-I C-III C-II NADH O2 FADH2 NAD+ H2O FAD

  23. NDI1 mimics complex I and AOX bypasses complex III and complex IV. H+ H+ H+ Cyt c Q C-III C-I C-IV NDI1 NADH AOX C-II O2 FADH2 NAD+ H2O NADH O2 FAD H2O NAD+ Eric Dufor

  24. NDI1 and AOX expression uncouples electron flux from proton pumping in cells with depleted mitochondrial DNA. Q AOX NDI1 C-II NADH O2 H2O FADH2 NAD+ FAD

  25. AOX-NDI1 expression restores electron flux but not membrane potential. NDI/ AOX NADH/FADH2 O2 H2O TCA ATP4- ADP3- NAD+/FAD Y Metabolites

  26. AOX-NDI expression does not restore mitochondrial DNA.

  27. AOX-NDI expression restores oxygen consumption rate in isolated mitochondria. Seahorse Biosciences

  28. Study of the metabolic profile of the cells DN-POLG-GFP/BFP Day 0 DN-POLG-GFP/BFP Day 3 DN-POLG-GFP/BFP Day 6 DN-POLG-GFP/BFP Day 9 DN-POLG-AOX/NDI1 Day 0 DN-POLG-AOX/NDI1 Day 3 DN-POLG-AOX/NDI1 Day 6 DN-POLG-AOX/NDI1 Day 9 Amino Acid Carbohydrate Cofactors and Vitamins Energy Lipid Nucleotide Peptide Xenobiotics

  29. Study of the metabolic profile of the cells

  30. AOX-NDI expression maintains levels of TCA cycle metabolites.

  31. AOX-NDI does NOT restore mitochondrial membrane potential.

  32. AOX-NDI1 expression restores electron flux (TCA cycle) but not membrane potential. NDI/ AOX NADH/FADH2 O2 H2O TCA ATP4- ADP3- NAD+/FAD Y Metabolites

  33. Is electron flux (TCA cycle) sufficient to restore cell proliferation and histone acetylation?

  34. Electron flux (TCA cycle) is sufficient to restore histone acetylation. DN-POLG-AOX/NDI1 0 3 6 9 Days DOX - + + + H3K9ac H3K14ac H3K18ac H3K27ac H3 total

  35. Electron flux (TCA cycle) is NOT sufficient to restore cell proliferation.

  36. Electron flux (TCA cycle) is NOT sufficient to restore increased glucose catabolism.

  37. Electron flux (TCA cycle) is NOT sufficient to restore glucose dependency for survival.

  38. Electron flux without proton pumping is NOT sufficient to alleviate energetic stress. DN-POLG-AOX/NDI1 Days 0 0 3 3 6 6 9 9 - - + + + + + + DOX p-AMPK AMPK Actin

  39. Two functions of mitochondria: TCA cycle metabolites and membrane potential. H+ ETC NADH/FADH2 O2 H2O H+ TCA ADP ATP NAD+/FAD H+ ? Y Histone Acetylation Cell Proliferation

  40. Acknowledgements Chandel Lab NavChandel Sam Weinberg Heywon Kong Lauren Diebold James Eisenbart MananMetha Colleen Reczek Arianne Rodriguez Michael Schieber Collaborators He Huang Yingming Zhao Ty Wang Janine Santos Eric Dufor Hans Spelbrink Ralph Deberardinis

  41. Loss of ATPIF1 allows the maintenance of mitochondrial membrane potential

  42. Loss of mitochondrial DNA decreased mitochondrial mass.

  43. Loss of mitochondrial DNA alters mitochondrial morphology

  44. Let Us MeetAgain Wewelcomeyoualltoourfutureconferencesof OMICS International Please Visit: www.metabolomicsconference.com www.conferenceseries.com http://www.conferenceseries.com/clinical-research-conferences.php

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