Navdeep S Chandel

Summary

Affiliation: Northwestern University
Country: USA

Publications

  1. pmc The good and the bad of antibiotics
    Navdeep S Chandel
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Sci Transl Med 5:192fs25. 2013
  2. pmc Metabolic changes in cancer cells upon suppression of MYC
    Elena Anso
    Department of Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA
    Cancer Metab 1:7. 2013
  3. doi request reprint Evolution of Mitochondria as Signaling Organelles
    Navdeep S Chandel
    Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA Electronic address
    Cell Metab 22:204-6. 2015
  4. pmc Targeting glucose metabolism for cancer therapy
    Robert B Hamanaka
    Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    J Exp Med 209:211-5. 2012
  5. pmc The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production
    Eric L Bell
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    J Cell Biol 177:1029-36. 2007
  6. pmc Mitochondria as signaling organelles
    Navdeep S Chandel
    Section of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    BMC Biol 12:34. 2014
  7. doi request reprint Mitochondrial regulation of oxygen sensing
    Navdeep S Chandel
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, IL, 606011, USA
    Adv Exp Med Biol 661:339-54. 2010
  8. pmc Mitochondrial complex III: an essential component of universal oxygen sensing machinery?
    Navdeep S Chandel
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Respir Physiol Neurobiol 174:175-81. 2010
  9. pmc Hypoxia leads to Na,K-ATPase downregulation via Ca(2+) release-activated Ca(2+) channels and AMPK activation
    Galina A Gusarova
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Cell Biol 31:3546-56. 2011
  10. pmc Mitochondrial complex III-generated oxidants activate ASK1 and JNK to induce alveolar epithelial cell death following exposure to particulate matter air pollution
    Saul Soberanes
    Division of Pulmonary and Critical Care Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 284:2176-86. 2009

Research Grants

Collaborators

Detail Information

Publications91

  1. pmc The good and the bad of antibiotics
    Navdeep S Chandel
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Sci Transl Med 5:192fs25. 2013
    ..Bactericidal antibiotics with diverse mechanisms of action induce generation of mitochondrial reactive oxygen species in mammalian cells (Kalghatgi et al., this issue). ..
  2. pmc Metabolic changes in cancer cells upon suppression of MYC
    Elena Anso
    Department of Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA
    Cancer Metab 1:7. 2013
    ..However, metabolic differences between MYC-dependent cancer cells and their isogenic differentiated counterparts have not been characterized upon MYC suppression in vitro...
  3. doi request reprint Evolution of Mitochondria as Signaling Organelles
    Navdeep S Chandel
    Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA Electronic address
    Cell Metab 22:204-6. 2015
    ..Thus, the signaling function of the mitochondria may have been selected by nature from the inception of the early eukaryote, as discussed in this essay. ..
  4. pmc Targeting glucose metabolism for cancer therapy
    Robert B Hamanaka
    Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    J Exp Med 209:211-5. 2012
    ..It is anticipated that understanding which metabolic enzymes are particularly critical for tumor cell proliferation and survival will identify novel therapeutic targets...
  5. pmc The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production
    Eric L Bell
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    J Cell Biol 177:1029-36. 2007
    ..These results provide genetic and pharmacologic evidence that the Qo site of complex III is required for the transduction of hypoxic signal by releasing ROS to stabilize the HIF-1alpha protein...
  6. pmc Mitochondria as signaling organelles
    Navdeep S Chandel
    Section of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    BMC Biol 12:34. 2014
    ..This review is a brief account of recent work in mitochondria-dependent signaling in the historical framework of the early studies. ..
  7. doi request reprint Mitochondrial regulation of oxygen sensing
    Navdeep S Chandel
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, IL, 606011, USA
    Adv Exp Med Biol 661:339-54. 2010
    ..Here we outline the model in which mitochondrial complex III regulate the activity of HIF and diminish ATP utilization processes through the increased production of ROS during hypoxia...
  8. pmc Mitochondrial complex III: an essential component of universal oxygen sensing machinery?
    Navdeep S Chandel
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Respir Physiol Neurobiol 174:175-81. 2010
    ..Here I propose a model wherein complex III is integral to oxygen sensing in regulating diverse response to hypoxia...
  9. pmc Hypoxia leads to Na,K-ATPase downregulation via Ca(2+) release-activated Ca(2+) channels and AMPK activation
    Galina A Gusarova
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Cell Biol 31:3546-56. 2011
    ..These data suggest that during hypoxia, calcium entry via CRAC channels leads to AMPK activation, Na,K-ATPase downregulation, and alveolar epithelial dysfunction...
  10. pmc Mitochondrial complex III-generated oxidants activate ASK1 and JNK to induce alveolar epithelial cell death following exposure to particulate matter air pollution
    Saul Soberanes
    Division of Pulmonary and Critical Care Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 284:2176-86. 2009
    ..We conclude that particulate matter air pollution induces the generation of ROS primarily from site III of the mitochondrial electron transport chain and that these ROS activate the intrinsic apoptotic pathway through ASK1, JNK, and p53...
  11. pmc Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio
    Brooke M Emerling
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Free Radic Biol Med 46:1386-91. 2009
    ..Collectively, these data indicate that oxidative stress and not an increase in the AMP/ATP ratio is required for hypoxic activation of AMPK...
  12. pmc Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS
    Tatyana A Klimova
    Department of Medicine, Northwestern University, Chicago, Illinois, USA
    FASEB J 23:783-94. 2009
    ..Collectively, these results indicate a ROS-independent but p53/pRb-dependent senescence mechanism during hyperoxia...
  13. pmc Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death
    Joslyn K Brunelle
    Department of Medicine, Northwestern University Medical School, 240 East Huron Avenue, Chicago, IL 60611, USA
    Mol Cell Biol 27:1222-35. 2007
    ..Collectively, these results demonstrate that anoxia-induced cell death requires the loss of Mcl-1 protein and inhibition of the electron transport chain to negate Bcl-X(L)/Bcl-2 proteins...
  14. ncbi request reprint Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak
    Nathan Majewski
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Mol Cell 16:819-30. 2004
    ....
  15. pmc Epithelial cell death is an important contributor to oxidant-mediated acute lung injury
    G R Scott Budinger
    Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL 60611, USA
    Am J Respir Crit Care Med 183:1043-54. 2011
    ..Acute lung injury and the acute respiratory distress syndrome are characterized by increased lung oxidant stress and apoptotic cell death. The contribution of epithelial cell apoptosis to the development of lung injury is unknown...
  16. pmc Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis
    Gabriel Loor
    Department of Surgery, University of Chicago, Chicago, IL 60637, USA
    Free Radic Biol Med 49:1925-36. 2010
    ..These studies suggest that multiple redundant cell death pathways are activated by menadione, but that PARP plays an essential role in mediating each of them...
  17. pmc Mitochondrial reactive oxygen species promote epidermal differentiation and hair follicle development
    Robert B Hamanaka
    Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Sci Signal 6:ra8. 2013
    ..These findings indicate that mitochondria-generated ROS are critical mediators of cellular differentiation and tissue morphogenesis...
  18. pmc Mitochondrial oxidant stress triggers cell death in simulated ischemia-reperfusion
    Gabriel Loor
    Department of Surgery, University of Chicago, Chicago, IL 60637, USA
    Biochim Biophys Acta 1813:1382-94. 2011
    ..Therefore, mitochondrial apoptosis appears to represent a redundant death pathway in this model of simulated I/R. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection...
  19. doi request reprint Keratinocyte growth factor expression is suppressed in early acute lung injury/acute respiratory distress syndrome by smad and c-Abl pathways
    Navdeep S Chandel
    Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Crit Care Med 37:1678-84. 2009
    ..We wished to determine whether acute lung injury/acute respiratory distress syndrome (ALI/ARDS) alveolar fluid induces KGF and fibroblast genes important for alveolar repair...
  20. pmc Mitochondrial complex III ROS regulate adipocyte differentiation
    Kathryn V Tormos
    Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Cell Metab 14:537-44. 2011
    ..These results indicate that mitochondrial metabolism and ROS generation are not simply a consequence of differentiation but are a causal factor in promoting adipocyte differentiation...
  21. ncbi request reprint Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells
    Leonard J Buccellato
    Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 279:6753-60. 2004
    ..Bax activation at the mitochondrial membrane requires the generation of ROS and can be prevented by the overexpression of Bcl-XL...
  22. pmc AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress
    Sang Min Jeon
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Nature 485:661-5. 2012
    ....
  23. ncbi request reprint Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway
    Vivian Y Lee
    Div of Pulmonary and Critical Care, Northwestern University, Chicago, IL 60611, USA
    Am J Physiol Lung Cell Mol Physiol 289:L521-8. 2005
    ..These data indicate that bleomycin induces cell death through a JNK-dependent mitochondrial death pathway in alveolar epithelial cells...
  24. pmc Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
    Frank Weinberg
    Division of Pulmonary and Critical Care, Department of Medicine, Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 107:8788-93. 2010
    ..These results demonstrate that mitochondrial metabolism and mitochondrial ROS generation are essential for Kras-induced cell proliferation and tumorigenesis...
  25. pmc Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation
    Daniela Urich
    Feinberg School of Medicine, Northwestern University, Division of Pulmonary and Critical Care Medicine, 240 E Huron, Chicago, IL 60611, USA
    FASEB J 23:2055-64. 2009
    ..We conclude that PM(2.5)-induced cell death requires Noxa both in vitro and in vivo and that Noxa-dependent cell death might contribute to PM-induced alveolar epithelial dysfunction and the resulting inflammatory response...
  26. pmc Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family members
    Colleen M Snyder
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois, United States of America
    PLoS ONE 4:e7059. 2009
    ..However, scavengers of ROS or peroxynitrite do not prevent NO-induced cell death. Collectively, these data indicate that NO degrades MCL-1 through the ASK1-JNK1 axis to induce BAX/BAK-dependent cell death...
  27. pmc Mitochondrial reactive oxygen species regulate transforming growth factor-β signaling
    Manu Jain
    Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Biol Chem 288:770-7. 2013
    ..Collectively, our results indicate that mitochondrial ROS are essential for normal TGF-β-mediated gene expression and that targeting mitochondrial ROS might be beneficial in diseases associated with excessive fibrosis...
  28. pmc Alcohol worsens acute lung injury by inhibiting alveolar sodium transport through the adenosine A1 receptor
    Laura Dada
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
    PLoS ONE 7:e30448. 2012
    ..We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung...
  29. pmc Alpha1-AMP-activated protein kinase regulates hypoxia-induced Na,K-ATPase endocytosis via direct phosphorylation of protein kinase C zeta
    Galina A Gusarova
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E Huron, McGaw M 300, Chicago, IL 60611, USA
    Mol Cell Biol 29:3455-64. 2009
    ..Accordingly, we provide the first evidence that hypoxia-generated mitochondrial ROS lead to the activation of the AMPK alpha1 isoform, which binds and directly phosphorylates PKC zeta at Thr410, thereby promoting Na,K-ATPase endocytosis...
  30. ncbi request reprint Anoxia-induced apoptosis occurs through a mitochondria-dependent pathway in lung epithelial cells
    Matthew T Santore
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, 300 E Superior Street, Chicago, IL 60601, USA
    Am J Physiol Lung Cell Mol Physiol 282:L727-34. 2002
    ..These results indicate that A549 cells require a functional electron transport chain and the release of cytochrome c for anoxia-induced apoptosis...
  31. pmc BH3 peptides induce mitochondrial fission and cell death independent of BAX/BAK
    Emelyn H Shroff
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois, United States of America
    PLoS ONE 4:e5646. 2009
    ..These results suggest that pro-survival BCL-2 proteins regulate mitochondrial fission and cell death in the absence of BAX and BAK...
  32. ncbi request reprint c-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia-inducible factor-1
    Joslyn K Brunelle
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611 3010, USA
    J Biol Chem 279:4305-12. 2004
    ..Thus, oxygen deprivation-induced cell death in fibroblasts with deregulated expression of c-Myc is independent of p53 or HIF-1 status, but is dependent on the Bcl-2 family member Bax or Bak to initiate mitochondrial dependent cell death...
  33. pmc Proapoptotic Bid is required for pulmonary fibrosis
    G R Scott Budinger
    Department of Medicine, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 103:4604-9. 2006
    ..These results indicate that Bcl-2 family members are critical regulators for the development of pulmonary fibrosis downstream of TGF-beta1 activation...
  34. pmc Proteasomal inhibition after injury prevents fibrosis by modulating TGF-β(1) signalling
    Gokhan M Mutlu
    Department of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Thorax 67:139-46. 2012
    ..It is hypothesised that proteasomal inhibition would prevent lung and skin fibrosis after injury by inhibiting TGF-β(1)-mediated transcription...
  35. ncbi request reprint The intrinsic apoptotic pathway is required for lipopolysaccharide-induced lung endothelial cell death
    Helena L Wang
    Division of Pulmonary and Critical Care Medicine, Loyola University, Maywood, Illinois 60153, USA
    J Immunol 179:1834-41. 2007
    ..We conclude that LPS and cycloheximide-induced death in HmVECs requires the intrinsic cell death pathway, but not the generation of reactive oxygen species...
  36. ncbi request reprint Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species
    Clara Schroedl
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Am J Physiol Lung Cell Mol Physiol 283:L922-31. 2002
    ..Rotenone inhibited hypoxic, but not anoxic, stabilization of HIF-1alpha protein. These results indicate that a functional electron transport chain is required for hypoxic but not anoxic stabilization of HIF-1alpha protein...
  37. pmc Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia
    Eric L Bell
    The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Mol Cell Biol 27:5737-45. 2007
    ..These findings provide genetic evidence that hypoxia utilizes mitochondrial ROS as signaling molecules to activate HIF-dependent extension of replicative life span...
  38. pmc Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follic
    Hena Alam
    Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA
    J Biol Chem 279:19431-40. 2004
    ..These results show that FSH enhances HIF-1 activity downstream of the PI 3-kinase/AKT/Rheb/mTOR pathway in GCs and that HIF-1 activity is necessary for FSH to induce multiple follicular differentiation markers...
  39. pmc microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation
    Han Peng
    Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 109:14030-4. 2012
    ..Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus...
  40. pmc Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling
    Brooke M Emerling
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Mol Cell Biol 25:4853-62. 2005
    ..These results provide genetic evidence that p38 mitogen-activated protein kinase signaling is essential for HIF-1 activation...
  41. pmc Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-zeta
    Laura A Dada
    Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Clin Invest 111:1057-64. 2003
    ..Accordingly, we provide evidence that hypoxia decreases Na,K-ATPase activity in AEC by triggering its endocytosis through mitochondrial ROS and PKC-zeta-mediated phosphorylation of the Na,K-ATPase alpha(1) subunit...
  42. ncbi request reprint Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
    Joslyn K Brunelle
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Cell Metab 1:409-14. 2005
    ..These findings provide genetic evidence that oxygen sensing is dependent on mitochondrial-generated reactive oxygen species (ROS) but independent of oxidative phosphorylation...
  43. pmc Airborne particulate matter inhibits alveolar fluid reabsorption in mice via oxidant generation
    Gokhan M Mutlu
    Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL 60611, USA
    Am J Respir Cell Mol Biol 34:670-6. 2006
    ..The intratracheal instillation of particulate matter results in alveolar epithelial injury and decreased alveolar fluid clearance, conceivably due to downregulation of the Na,K-ATPase...
  44. pmc The role of nuclear lamin B1 in cell proliferation and senescence
    Takeshi Shimi
    Department of Cell and Molecular Biology, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Genes Dev 25:2579-93. 2011
    ..This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway...
  45. doi request reprint Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments
    Ni Na
    Northwestern University Medical School, Pulmonary and Critical Care Medicine, 240 East Huron, McGaw 2328, Chicago, IL 60611, USA
    FASEB J 24:799-809. 2010
    ..Na, N., Chandel, N. S., Litvan, J., Ridge, K. M. Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments...
  46. ncbi request reprint Bronchoalveolar lavage fluid from patients with acute lung injury/acute respiratory distress syndrome induces myofibroblast differentiation
    Lauren Synenki
    Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL, USA
    Crit Care Med 35:842-8. 2007
    ..We wished to determine whether bronchoalveolar lavage fluid (BALF) from ALI/ARDS patients can induce myofibroblast differentiation and if this induction is associated with outcome...
  47. pmc AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na,K-ATPase endocytosis
    István Vadász
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Clin Invest 118:752-62. 2008
    ....
  48. pmc Bcl-2 family members and functional electron transport chain regulate oxygen deprivation-induced cell death
    David S McClintock
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60601 3010, USA
    Mol Cell Biol 22:94-104. 2002
    ..Proapoptotic Bcl-2 family members and a functional electron transport chain are required to initiate cell death in response to oxygen deprivation...
  49. pmc The proto-oncometabolite fumarate binds glutathione to amplify ROS-dependent signaling
    Lucas B Sullivan
    Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Mol Cell 51:236-48. 2013
    ..Increased ROS also correlates with hypermethylation of histones in these cells. Thus, fumarate serves as a proto-oncometabolite by binding to glutathione which results in the accumulation of ROS...
  50. pmc Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling
    Laura A Sena
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    Immunity 38:225-36. 2013
    ..Thus, mitochondrial metabolism is a critical component of T cell activation through the production of complex III ROS...
  51. pmc Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis
    Robert D Guzy
    Department of Pediatrics, Northwestern University, 303 East Chicago Ave, Ward Bldg 12 191, Chicago, IL 60611
    Mol Cell Biol 28:718-31. 2008
    ..Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA...
  52. ncbi request reprint Role of Bcl-2 family members in anoxia induced cell death
    Emelyn H Shroff
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Cell Cycle 6:807-9. 2007
    ..Second, cells inhibit the mitochondrial electron transport chain to negate the pro-survival function of Bcl-2/Bcl-X(L). These observations indicate that loss of pro-survival function is necessary for anoxia induced cell death...
  53. pmc Elevated CO(2) levels cause mitochondrial dysfunction and impair cell proliferation
    Christine U Vohwinkel
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 286:37067-76. 2011
    ..These results are of relevance to patients with hypercapnia such as those with chronic obstructive pulmonary disease, asthma, cystic fibrosis, bronchopulmonary dysplasia, and muscular dystrophies...
  54. pmc Leptin resistance protects mice from hyperoxia-induced acute lung injury
    Amy Bellmeyer
    Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Am J Respir Crit Care Med 175:587-94. 2007
    ..Human data suggest that the incidence of acute lung injury is reduced in patients with type II diabetes mellitus. However, the mechanisms by which diabetes confers protection from lung injury are unknown...
  55. ncbi request reprint Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system
    Alejandro P Comellas
    Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Circ Res 98:1314-22. 2006
    ..Accordingly, we provide evidence that during hypoxia, mitochondrial reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase via the ubiquitin-conjugating system...
  56. ncbi request reprint Mitochondrial regulation of oxygen sensing
    Eric L Bell
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago IL 606011, USA
    Mitochondrion 5:322-32. 2005
    ..How cells sense decrease in oxygen levels to elicit an increase in HIF dependent gene expression is not fully understood. In this review, we discuss the role of mitochondria as oxygen sensors regulating HIF...
  57. pmc Leptin promotes fibroproliferative acute respiratory distress syndrome by inhibiting peroxisome proliferator-activated receptor-γ
    Manu Jain
    Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Am J Respir Crit Care Med 183:1490-8. 2011
    ..Diabetic patients have a lower incidence of acute respiratory distress syndrome (ARDS), and those who develop ARDS are less likely to die. The mechanisms that underlie this protection are unknown...
  58. ncbi request reprint Hypoxia-mediated Na-K-ATPase degradation requires von Hippel Lindau protein
    Guofei Zhou
    Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E Huron, Chicago, IL 60611, USA
    FASEB J 22:1335-42. 2008
    ..These findings suggest that pVHL participates in the hypoxia-mediated degradation of plasma membrane Na-K-ATPase in a HIF-independent manner...
  59. ncbi request reprint Hyperoxia-induced apoptosis does not require mitochondrial reactive oxygen species and is regulated by Bcl-2 proteins
    G R Scott Budinger
    Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Biol Chem 277:15654-60. 2002
    ..The mitochondrial generation of reactive oxygen species is not required for cell death following exposure to hyperoxia...
  60. pmc Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
    William W Wheaton
    Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, United States
    elife 3:e02242. 2014
    ..Thus, we have demonstrated that metformin's inhibitory effects on cancer progression are cancer cell autonomous and depend on its ability to inhibit mitochondrial complex I.DOI: http://dx.doi.org/10.7554/eLife.02242.001. ..
  61. ncbi request reprint Hypoxia sensitizes cells to nitric oxide-induced apoptosis
    Vivian Y Lee
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Biol Chem 277:16067-74. 2002
    ....
  62. ncbi request reprint Oxygen sensing: getting pumped by sterols
    Brooke M Emerling
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Sci STKE 2005:pe30. 2005
    ..It is not yet clear whether this mechanism is involved in the mammalian response to hypoxia, possibly in conjunction with activation of one or both of the hypoxia-inducible factor (HIF-1 or HIF-2) transcription factors...
  63. pmc Asbestos-induced alveolar epithelial cell apoptosis. The role of endoplasmic reticulum stress response
    David W Kamp
    1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Jesse Brown Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois and
    Am J Respir Cell Mol Biol 49:892-901. 2013
    ..These results show that asbestos triggers an AEC ER stress response and subsequent intrinsic apoptosis that is mediated in part by ER Ca²(2+) release. ..
  64. pmc Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung
    Matthew C Duch
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States
    Nano Lett 11:5201-7. 2011
    ....
  65. pmc Mitochondrial regulation of cell survival and death during low-oxygen conditions
    Colleen M Snyder
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, Illinois, USA
    Antioxid Redox Signal 11:2673-83. 2009
    ..5-3% O2), mitochondrial oxidative stress activates hypoxia-inducible factors (HIFs) to promote cell survival. In this review, we discuss how mitochondria, BCL-2 proteins, and HIFs are crucial for cellular responses to low oxygen...
  66. ncbi request reprint Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes
    Hirotaro Iwase
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Free Radic Biol Med 43:590-9. 2007
    ..This response is associated with a remarkable attenuation of cell death, suggesting that ischemic cell death may be a regulated event...
  67. ncbi request reprint Genetics of mitochondrial electron transport chain in regulating oxygen sensing
    Eric L Bell
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA
    Methods Enzymol 435:447-61. 2007
    ..This chapter outlines methods used to explore the role of the electron transport chain and a by-product of electron transport, reactive oxygen species, in oxygen sensing...
  68. doi request reprint Reactive oxygen species-dependent signaling regulates cancer
    Frank Weinberg
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Cell Mol Life Sci 66:3663-73. 2009
    ..Here we review the role of redox-dependent signaling pathways and transcription factors that regulate tumorigenesis...
  69. pmc Rethinking antioxidants in the intensive care unit
    Manu Jain
    1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    Am J Respir Crit Care Med 188:1283-5. 2013
    ..In this perspective, we suggest that antioxidants likely interfere with the normal immune response, thus contributing to the lack of efficacy in patients with critical illness. ..
  70. ncbi request reprint Detection of oxygen-sensing properties of mitochondria
    Navdeep S Chandel
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Methods Enzymol 352:31-40. 2002
  71. ncbi request reprint Bcl-2 family members regulate anoxia-induced cell death
    Emelyn H Shroff
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Antioxid Redox Signal 9:1405-9. 2007
    ..The pathway is initiated by the loss of function of the prosurvival Bcl-2 family members Mcl-1 and Bcl-2/Bcl-XL, resulting in Bax- or Bak-dependent release of cytochrome c and subsequent caspase-9-dependent cell death...
  72. doi request reprint Mitochondrial metabolism and cancer
    Frank Weinberg
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611 2010, USA
    Ann N Y Acad Sci 1177:66-73. 2009
    ..Here we review the accumulating evidence that mitochondrial metabolism plays an essential role in tumor cell proliferation...
  73. pmc Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway
    Gokhan M Mutlu
    Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    J Clin Invest 117:2952-61. 2007
    ..These results provide a potential mechanism linking ambient particulate matter exposure and thrombotic events...
  74. ncbi request reprint Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis
    Vijayalakshmi Panduri
    Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 3010, USA
    Am J Physiol Lung Cell Mol Physiol 286:L1220-7. 2004
    ..Nonmitochondrial-associated ROS may also contribute to AEC apoptosis, particularly with high levels of asbestos exposure...
  75. ncbi request reprint Mitochondrial oxygen sensing: regulation of hypoxia-inducible factor by mitochondrial generated reactive oxygen species
    Eric L Bell
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Essays Biochem 43:17-27. 2007
    ..In this chapter we outline the model in which mitochondria regulate the stability of HIF through the increased production of ROS (reactive oxygen species) during hypoxia...
  76. pmc Inter-connection between mitochondria and HIFs
    Kathryn V Tormos
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611 2909, USA
    J Cell Mol Med 14:795-804. 2010
    ..In this review, we examine the evidence that mitochondria and HIFs are intimately connected to regulate each other resulting in appropriate responses to hypoxia...
  77. ncbi request reprint The cellular basis for diverse responses to oxygen
    Navdeep S Chandel
    Department of Medicine and Department of Cell and Molecular Biology, Northwestern University, McGaw Pavilion M 334, 240 East Huron Avenue, Chicago, IL 60611, USA
    Free Radic Biol Med 42:165-74. 2007
    ..This perspective reviews the role of signaling through mitochondrial ROS in hypoxic and hyperoxic environments...
  78. pmc Hypoxia. 2. Hypoxia regulates cellular metabolism
    William W Wheaton
    Division of Pulmonary and Critical Care Medicine, 240 East Huron Ave, McGraw M 334, Chicago, IL 60611 2909, USA
    Am J Physiol Cell Physiol 300:C385-93. 2011
    ..In this review, we discuss these mechanisms that diminish metabolic supply and demand for adaptation to hypoxia...
  79. pmc PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a)
    Brooke M Emerling
    Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 105:2622-7. 2008
    ..Coimmunoprecipitation and GAL4-HIF-1alpha transactivation assays reveal that FOXO3a interferes with p300-dependent HIF-1 transcriptional activity. Thus, FOXO3a negatively regulates HIF-1 transcriptional activity...
  80. pmc Stretch-induced activation of AMP kinase in the lung requires dystroglycan
    G R Scott Budinger
    Division of Pulmonary and Critical Care Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Am J Respir Cell Mol Biol 39:666-72. 2008
    ..These results suggest that exposure to cyclic stretch activates the metabolic sensing pathway AMPK in the lung epithelium and supports a novel role for dystroglycan in this mechanotransduction...
  81. pmc Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
    Robert B Hamanaka
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Trends Biochem Sci 35:505-13. 2010
    ....
  82. ncbi request reprint Targeting the mitochondria for cancer therapy: regulation of hypoxia-inducible factor by mitochondria
    Eric L Bell
    Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Antioxid Redox Signal 10:635-40. 2008
    ..Here we outline how mitochondria regulate the activity of HIF during hypoxia...
  83. pmc Mitochondrial reactive oxygen species regulate hypoxic signaling
    Robert B Hamanaka
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Curr Opin Cell Biol 21:894-9. 2009
    ..The following is a brief overview of the current understanding of the role of mitochondrial-produced ROS in cellular oxygen signaling...
  84. ncbi request reprint Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes
    Andre Kulisz
    Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Am J Physiol Lung Cell Mol Physiol 282:L1324-9. 2002
    ....
  85. ncbi request reprint Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury
    G R Scott Budinger
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, 240 East Huron, Chicago, IL 60611, USA
    Intensive Care Med 31:121-8. 2005
    ..We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes...
  86. pmc Biocompatible nanoscale dispersion of single-walled carbon nanotubes minimizes in vivo pulmonary toxicity
    Gokhan M Mutlu
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Evanston, IL 60208, USA
    Nano Lett 10:1664-70. 2010
    ..Biocompatible nanoscale dispersion provides a scalable method to generate purified preparations of SWCNTs with minimal toxicity, thus allowing them to be used safely in commercial and biomedical applications...
  87. pmc A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation
    Xiaoyu Lin
    Cancer Research and Advanced Technology, Global Pharmaceutical Research and Development, AP10, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 105:174-9. 2008
    ..These results also suggest that targeting mitochondrial ROS production might be a highly effective way of blocking HIF-1 activity in tumors...
  88. ncbi request reprint Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation
    Joan S Lewis
    Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    J Natl Cancer Inst 97:1746-59. 2005
    ..Here, we investigated the role of the mitochondrial apoptotic pathway in this process...
  89. pmc Compound C inhibits hypoxic activation of HIF-1 independent of AMPK
    Brooke M Emerling
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    FEBS Lett 581:5727-31. 2007
    ..Furthermore, we demonstrate that Compound C functions as a repressor of HIF-1 by inhibiting respiration and suppressing mitochondrial generated ROS...

Research Grants2

  1. Mechanisms of Replicative Senescence of lung cells during hypoxia.
    Navdeep Chandel; Fiscal Year: 2007
    ..Collectively these studies will provide new information regarding mechanisms underlying replicative senescence and the aging process. [unreadable] [unreadable] [unreadable]..
  2. Mechanisms of HIF activation in pulmonary vasculature.
    Navdeep Chandel; Fiscal Year: 2008
    ..unreadable] [unreadable]..