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Kasturi Mitra, PhD

Kasturi Mitra, PhD
 
Assistant Professor
Department of Genetics
KAUL 740B Zip 0024
Phone: (205) 996-4178
E-mail: kasturi@uab.edu

Research Interest

Towards understanding the structure-function relationship of mitochondria in health and disease
Mitochondria are the cellular organelles that became the seat of energy production and intermediary metabolism during the course of evolution of eukaryotic cells. They are also crucial players in redox balance, calcium homeostasis, lipid modification and regulation of cell death in various developmental contexts. In various cells mitochondrial structure has been found to be dynamic. They exist in different inter-convertible forms resulting from fission-fusion events between individual mitochondria, significance of which is far from clear. Our long term interest lies in understanding the structure-function relationship of these multifunctional organelles. Currently, we are focused in understanding the significance of mitochondrial dynamism in cell proliferation and differentiation. A set of proteins that govern either fusion or fission of mitochondrial inner and outer membranes have been characterized and it is their activities that decide the steady state mitochondrial morphology in a cell; when fission dominates mitochondria remain as small fragmented elements and when fusion dominates mitochondria remain coalesced into larger hyperfused forms. In mitotic cells the key cell cycle regulators modulate mitochondrial morphology during progression through a mitotic cycle cell cycle, which in turn modulates cell cycle (Figure). We use various kinds of biochemical, cell biological, microscopy and genetic tools to understand if the mitochondrial fission-fusion proteins can regulate cell proliferation, deregulation of which could initiate or maintain tumorigenic processes.

Ongoing Projects

  1. Regulation of Cyclin E by mitochondria
  2. Involvement of DRP1 driven mitochondrial fission in establishing tumor heterogeneity in epithelial ovarian cancer
  3. Role of DRP1 driven mitochondrial fission in ovarian epithelial cell layer development
  4. Effect of high sugar diet on cell proliferation in the absence of DRP1
  5. Real time effect of mitochondrial fission and fusion on energetics

Website:

Publications

  1. Tanwar DK, Parker DJ, Gupta P, Spurlock B, Alvarez RD, Basu MK*, Mitra K*. (2016). Crosstalk between the mitochondrial fission protein, Drp1, and the cell cycle is identified across various cancer types and can impact survival of epithelial ovarian cancer patients. Oncotarget. 2016 Aug 4. doi: 10.18632/oncotarget.11047. [Epub ahead of print] *corresponding authors
  2. Parker, D. J., Iyer, A., Shah, S., Moran, A., Hjelmeland, A. B., Basu, M. K., ... & Mitra, K. (2015). A new mitochondrial pool of cyclin E, regulated by Drp1, is linked to cell-density-dependent cell proliferation. J Cell Sci, 128(22), 4171-4182.
  3. Mitra K. Mitochondrial fission-fusion at the crossroads of proliferation and differentiation. Bioessays. 2013 Aug 14. doi: 10.1002/bies.201300011. PMID:23943303
  4. Mitchell T, Johnson MS, Ouyang X, Chacko BK, Mitra K, Lei X, Gai Y, Moore DR, Barnes S,  Zhang J, Koizumi A, Ramanadham S and Darley-Usmar VM. Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita+/Ins2-derived β-  cells. Am J Physiol Endocrinol Metab; published ahead of print July 2, 2013. PMID:23820623
  5. Fu., D., Mitra K., Sengupta P., Lippincott-Schwartz J., Arias I. Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization.Proc Natl Acad Sci U S A. 2013 Apr 15. PMID:23589864
  6. Rappole C. A., Mitra K., Wen H., Dynamic fluorescence imaging of the free radical products of X-ray absorption in live cells. Optical Nanoscopy, 2012, 1: 5
  7. Mitra K., Rikhy R., Lilly L., Lippincott-Schwartz J. DRP1 driven mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis. J. Cell Bio, 2012, May14; 197(4): 487-97 Highlighted in the news and views in the same issue and Faculty of 1000. PMID:22584906
  8. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell. 2010 May 14;141(4):656-67. Highlighted in Nat Rev Mol Cell Biol. and Cell.  PMID:20478256
  9. Mitra K, Lippincott-Schwartz J. Analysis of mitochondrial dynamics and functions using imaging approaches. Curr Protoc Cell Biol. 2010 Mar;Chapter 4:Unit 4.25.1-21.PMID:20235105
  10. Mitra K. Mitochondria, in The Liver: Biology and Pathobiology, 2009, Fifth Edition (ed I. M. Arias), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470747919.ch9
  11. Mitra K., Wunder Christian., Roysam B., Lin G., Lippincott-Schwartz J. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11960-5. Highlighted in PNAS cover page and in News and Views. PMID:19617534
  12. Shivaji S., Kumar V., Mitra K., Jha KN. Mammalian sperm capacitation: role of phosphotyrosine proteins. Soc Reprod Fertil Suppl. 2007;63:295-312.PMID:17566280
  13. Mitra K. and Shivaji,S., Proteins implicated in sperm capacitation. Indian J Exp Biol. 2005 Nov;43(11):1001-15.PMID:16313063
  14. Mitra K., Rangaraj N. and Shivaji S. Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa: correlation of its localization, tyrosine phosphorylation, and activity during sperm capacitation. J Biol Chem. 2005 Jul 8;280(27):25743-53.PMID:15888450
  15. Mitra K. and Shivaji S. Novel tyrosine-phosphorylated post-pyruvate metabolic enzyme, dihydrolipoamide dehydrogenase, involved in capacitation of hamster spermatozoa. Biol Reprod. 2004 Apr;70(4):887-99.PMID:14645106