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NARAYAN G. AVADHANI, B.Sc., Ph.D.
Harriet Ellison Woodward Professor of Biochemistry, University of Pennsylvania

Research Areas: Autoimmune diseases, Metabolic Regulation, Mitochondrial genetics, Mitochondrial function
PubMed Link
Contact Information:
3800 Spruce Street
Room 189E Vet
 Phone 215-898-8819
 Fax 215-573-6651
 Email narayan@vet.upenn.edu

The research in Dr. Avadhani's laboratory is focused on the following aspects of mitochondrial genetics and regulation of mitochondrial membrane biogenesis in mammalian cells:

1. Mechanisms of dual targeting of cytochrome P450 and related proteins to ER and mitochondria and mechanisms of activation of the chimeric N-terminal signal by cAMP and other physiological factors.

2. Characterization of a novel mitochondria-to-nucleus stress signaling in cells subjected to mitochondrial specific genetic, and or, metabolic stress, which operates through altered [Ca2+]c, and the role of mitochondrial stress signaling in tumor progression and metastasis.

3. Regulation of cytochrome oxidase gene expression, and modulation of enzyme assembly/activity under chemical and oxidative stress conditions.

4. Role of mitochondrial stress signaling in Embryonic Stem Cell function/differentiation, and mammalian mitochondrial transcription under chemical and oxidative stress in ES cells.

Srinivasan, Satish. Avadhani, Narayan G. Hypoxia-mediated mitochondrial stress in RAW264.7 cells induces osteoclast-like TRAP-positive cells. Annals of the New York Academy of Sciences 1117: 51-61, 2007.

Biswas, Gopa. Srinivasan, Satish. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G. Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling. Proceedings of the National Academy of Sciences of the United States of America 105: 186-91, 2008.

Sepuri, Naresh B V. Yadav, Sanjay. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G. Mitochondrial targeting of intact CYP2B1 and CYP2E1 and N-terminal truncated CYP1A1 proteins in Saccharomyces cerevisiae--role of protein kinase A in the mitochondrial targeting of CYP2E1. FEBS Journal 274: 4615-30, 2007.

Hardy, Micael. Rockenbauer, Antal. Vasquez-Vivar, Jeannette. Felix, Christopher. Lopez, Marcos. Srinivasan, Satish. Avadhani, Narayan. Tordo, Paul. Kalyanaraman, B. Detection, characterization, and decay kinetics of ROS and thiyl adducts of mito-DEPMPO spin trap. Chemical Research in Toxicology 20: 1053-60, 2007.

Spear, Joseph F. Prabu, Subbuswamy K. Galati, Domenico. Raza, Haider. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G. beta1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning. American Journal of Physiology - Heart & Circulatory Physiology 292: H2459-66, 2007.

Guha, Manti. Srinivasan, Satish. Biswas, Gopa. Avadhani, Narayan G. Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress. Journal of Biological Chemistry 282: 14536-46, 2007.

Fang, Ji-Kang. Prabu, Subbuswamy K. Sepuri, Naresh B. Raza, Haider. Anandatheerthavarada, Hindupur K. Galati, Domenico. Spear, Joseph. Avadhani, Narayan G. Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion. FEBS Letters 581: 1302-10, 2007.

Dasari, Venkata Ramesh. Anandatheerthavarada, Hindupur K. Robin, Marie-Anne. Boopathi, Ettickan. Biswas, Gopa. Fang, Ji-Kang. Nebert, Daniel W. Avadhani, Narayan G. Role of protein kinase C-mediated protein phosphorylation in mitochondrial translocation of mouse CYP1A1, which contains a non-canonical targeting signal. Journal of Biological Chemistry 281: 30834-47, 2006.

Wang, Ying. Biswas, Gopa. Prabu, Subbuswamy K. Avadhani, Narayan G. Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate through increased mitochondrial translocation of protein kinase Calpha in C2C12 myocytes. Biochemical Pharmacology 72: 881-92, 2006.

Devi, Latha. Prabhu, Badanavalu M. Galati, Domenico F. Avadhani, Narayan G. Anandatheerthavarada, Hindupur K. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. Journal of Neuroscience 26: 9057-68, 2006.

Prabu, Subbuswamy K. Anandatheerthavarada, Hindupur K. Raza, Haider. Srinivasan, Satish. Spear, Joseph F. Avadhani, Narayan G. Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. Journal of Biological Chemistry 281: 2061-70, 2006.

Biswas, Gopa. Guha, Manti. Avadhani, Narayan G. Mitochondria-to-nucleus stress signaling in mammalian cells: nature of nuclear gene targets, transcription regulation, and induced resistance to apoptosis. Gene 354: 132-9, 2005.

Biswas, G. Anandatheerthavarada, H K. Avadhani, N G. Mechanism of mitochondrial stress-induced resistance to apoptosis in mitochondrial DNA-depleted C2C12 myocytes. Cell Death & Differentiation 12: 266-78, 2005.

Nikonova, Elena V. Vijayasarathy, Camasamudram. Zhang, Lin. Cater, Jacqueline R. Galante, Raymond J. Ward, Stephen E. Avadhani, Narayan G. Pack, Allan I. Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness. Sleep 28: 21-7, 2005.

Boopathi, Ettickan. Lenka, Nibedita. Prabu, Subbuswamy K. Fang, Ji-Kang. Wilkinson, Frank. Atchison, Michael. Giallongo, Agata. Avadhani, Narayan G. Regulation of murine cytochrome c oxidase Vb gene expression during myogenesis: YY-1 and heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP1) reciprocally regulate transcription activity by physical interaction with the BERF-1/ZBP-89 factor. Journal of Biological Chemistry 279: 35242-54, 2004.

Butow, Ronald A. Avadhani, Narayan G. Mitochondrial signaling: the retrograde response. [Review] [119 refs] Molecular Cell 14: 1-15, 2004.

Levy, Richard J. Vijayasarathy, C. Raj, Nichelle R. Avadhani, Narayan G. Deutschman, Clifford S. Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis. Shock 21: 110-4, 2004.

Iqbal Jameel, Sun Li, Cao Jay, Yuen Tony, Lu Ping, Bab Itai, Leu N Adrian, Srinivasan Satish, Wagage Sagie, Hunter Christopher A, Nebert Daniel W, Zaidi Mone, Avadhani Narayan G Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes. Proceedings of the National Academy of Sciences of the United States of America 110: 11115-20, 2013.

Bansal Seema, Anandatheerthavarada Hindupur K, Prabu Govindaswamy K, Milne Ginger L, Martin Martha V, Guengerich F Peter, Avadhani Narayan G Human cytochrome P450 2E1 mutations that alter mitochondrial targeting efficiency and susceptibility to ethanol-induced toxicity in cellular models. The Journal of biological chemistry 288: 12627-44, 2013.

Bajpai Prachi, Sangar Michelle C, Singh Shilpee, Tang Weigang, Bansal Seema, Chowdhury Goutam, Cheng Qian, Fang Ji-Kang, Martin Martha V, Guengerich F Peter, Avadhani Narayan G Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease. The Journal of biological chemistry 288: 4436-51, 2013.

Sleeper Meg M, Rosato Bradley P, Bansal Seema, Avadhani Narayan G Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy. American journal of veterinary research 73: 1759-64, 2012.

Srinivasan Satish, Avadhani Narayan G Cytochrome c oxidase dysfunction in oxidative stress. Free radical biology & medicine 53: 1252-63, 2012.

Tang Weigang, Chowdhury Anindya Roy, Guha Manti, Huang Li, Van Winkle Thomas, Rustgi Anil K, Avadhani Narayan G Silencing of IkBß mRNA causes disruption of mitochondrial retrograde signaling and suppression of tumor growth in vivo. Carcinogenesis 33: 1762-8, 2012.

Bansal Seema, Srinivasan Satish, Anandasadagopan Sureshkumar, Chowdhury Anindya Roy, Selvaraj Venkatesh, Kalyanaraman Balaraman, Joseph Joy, Avadhani Narayan G Additive effects of mitochondrion-targeted cytochrome CYP2E1 and alcohol toxicity on cytochrome c oxidase function and stability of respirosome complexes. The Journal of biological chemistry 287: 15284-97, 2012.

Ren Ling, Hong Sung-Hyeok, Chen Qing-Rong, Briggs Joseph, Cassavaugh Jessica, Srinivasan Satish, Lizardo Michael M, Mendoza Arnulfo, Xia Ashley Y, Avadhani Narayan, Khan Javed, Khanna Chand Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer research 72: 1001-12, 2012.

Avadhani Narayan G Targeting of the same proteins to multiple subcellular destinations: mechanisms and physiological implications. The FEBS journal 278: 4217, 2011.

Avadhani Narayan G, Sangar Michelle C, Bansal Seema, Bajpai Prachi Bimodal targeting of cytochrome P450s to endoplasmic reticulum and mitochondria: the concept of chimeric signals. The FEBS journal 278: 4218-29, 2011.

Yan Carol, Avadhani Narayan G, Iqbal Jameel The effects of smoke carcinogens on bone. Current osteoporosis reports 9: 202-9, 2011.

Raza Haider, Prabu Subbuswamy K, John Annie, Avadhani Narayan G Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats. International journal of molecular sciences 12: 3133-47, 2011.

Iqbal Jameel, Zaidi Mone, Avadhani Narayan G Cell signaling. Annals of the New York Academy of Sciences 1211: 3-8, 2010.

Guha Manti, Fang Ji-Kang, Monks Robert, Birnbaum Morris J, Avadhani Narayan G Activation of Akt is essential for the propagation of mitochondrial respiratory stress signaling and activation of the transcriptional coactivator heterogeneous ribonucleoprotein A2. Molecular biology of the cell 21: 3578-89, 2010.

Sondheimer Neal, Fang Ji-Kang, Polyak Erzsebet, Falk Marni J, Avadhani Narayan G Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial transcription. Biochemistry 49: 7467-73, 2010.

Sangar Michelle C, Bansal Seema, Avadhani Narayan G Bimodal targeting of microsomal cytochrome P450s to mitochondria: implications in drug metabolism and toxicity. Expert opinion on drug metabolism & toxicology 6: 1231-51, 2010.

Bansal Seema, Liu Chuan-Peng, Sepuri Naresh B V, Anandatheerthavarada Hindupur K, Selvaraj Venkatesh, Hoek Jan, Milne Ginger L, Guengerich F Peter, Avadhani Narayan G Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress. The Journal of biological chemistry 285: 24609-19, 2010.

Srinivasan Satish, Koenigstein Alexander, Joseph Joy, Sun Li, Kalyanaraman B, Zaidi Mone, Avadhani Narayan G Role of mitochondrial reactive oxygen species in osteoclast differentiation. Annals of the New York Academy of Sciences 1192: 245-52, 2010.

Guha Manti, Tang Weigang, Sondheimer Neal, Avadhani Narayan G Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets. Biochimica et biophysica acta 1797: 1055-65, 2010.

Sangar Michelle Cook, Anandatheerthavarada Hindupur K, Martin Martha V, Guengerich F Peter, Avadhani Narayan G Identification of genetic variants of human cytochrome P450 2D6 with impaired mitochondrial targeting. Molecular genetics and metabolism 99: 90-7, 2010.

Guha Manti, Pan Hua, Fang Ji-Kang, Avadhani Narayan G Heterogeneous nuclear ribonucleoprotein A2 is a common transcriptional coactivator in the nuclear transcription response to mitochondrial respiratory stress. Molecular biology of the cell 20: 4107-19, 2009.

Sangar Michelle Cook, Anandatheerthavarada Hindupur K, Tang Weigang, Prabu Subbuswamy K, Martin Martha V, Dostalek Miroslav, Guengerich F Peter, Avadhani Narayan G Human liver mitochondrial cytochrome P450 2D6--individual variations and implications in drug metabolism. The FEBS journal 276: 3440-53, 2009.

Anandatheerthavarada Hindupur K, Sepuri Naresh Babu V, Avadhani Narayan G Mitochondrial targeting of cytochrome P450 proteins containing NH2-terminal chimeric signals involves an unusual TOM20/TOM22 bypass mechanism. The Journal of biological chemistry 284: 17352-63, 2009.

Galati Domenico, Srinivasan Satish, Raza Haider, Prabu Subbuswamy K, Hardy Michael, Chandran Karunakaran, Lopez Marcos, Kalyanaraman Balaraman, Avadhani Narayan G Role of nuclear-encoded subunit Vb in the assembly and stability of cytochrome c oxidase complex: implications in mitochondrial dysfunction and ROS production. The Biochemical journal 420: 439-49, 2009.

Chandran Karunakaran, Aggarwal Deepika, Migrino Raymond Q, Joseph Joy, McAllister Donna, Konorev Eugene A, Antholine William E, Zielonka Jacek, Srinivasan Satish, Avadhani Narayan G, Kalyanaraman B Doxorubicin inactivates myocardial cytochrome c oxidase in rats: cardioprotection by Mito-Q. Biophysical journal 96: 1388-98, 2009.

Anandatheerthavarada Hindupur K, Sepuri Naresh Babu V, Biswas Gopa, Avadhani Narayan G An unusual TOM20/TOM22 bypass mechanism for the mitochondrial targeting of cytochrome P450 proteins containing N-terminal chimeric signals. The Journal of biological chemistry 283: 36060, 2008.

Wegrzyn Joanna, Potla Ramesh, Chwae Yong-Joon, Sepuri Naresh B V, Zhang Qifang, Koeck Thomas, Derecka Marta, Szczepanek Karol, Szelag Magdalena, Gornicka Agnieszka, Moh Akira, Moghaddas Shadi, Chen Qun, Bobbili Santha, Cichy Joanna, Dulak Jozef, Baker Darren P, Wolfman Alan, Stuehr Dennis, Hassan Medhat O, Fu Xin-Yuan, Avadhani Narayan, Drake Jennifer I, Fawcett Paul, Lesnefsky Edward J, Larner Andrew C Function of mitochondrial Stat3 in cellular respiration. Science (New York, N.Y.) 323: 793-7, 2009.

Dong Hongbin, Dalton Timothy P, Miller Marian L, Chen Ying, Uno Shigeyuki, Shi Zhanquan, Shertzer Howard G, Bansal Seema, Avadhani Narayan G, Nebert Daniel W Knock-in mouse lines expressing either mitochondrial or microsomal CYP1A1: differing responses to dietary benzo[a]pyrene as proof of principle. Molecular pharmacology 75: 555-67, 2009.

Boopathi Ettickan, Srinivasan Satish, Fang Ji-Kang, Avadhani Narayan G Bimodal protein targeting through activation of cryptic mitochondrial targeting signals by an inducible cytosolic endoprotease. Molecular cell 32: 32-42, 2008.

Biswas Gopa, Tang Weigang, Sondheimer Neal, Guha Manti, Bansal Seema, Avadhani Narayan G A distinctive physiological role for IkappaBbeta in the propagation of mitochondrial respiratory stress signaling. The Journal of biological chemistry 283: 12586-94, 2008.

Devi Latha, Raghavendran Vijayendran, Prabhu Badanavalu M, Avadhani Narayan G, Anandatheerthavarada Hindupur K Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. The Journal of biological chemistry 283: 9089-100, 2008.

B.Sc. (Chemistry/Physics) Karnatak Science College, 1962

Ph.D. (Biochemistry/Genetics) University of Bombay, 1969