Enrique Cadenas, MD, PhD

Dr. Cadenas received his M.D. and Ph.D. degrees from the University of Buenos Aires. He served as a research fellow at the Universities of Dundee (Scotland), Pennsylvania (USA) and Dusseldorf (Germany). Prior to coming to USC in 1989, Dr. Cadenas was an associate professor of pathology at the University of Linkoping (Sweden). Currently, he is a professor of molecular pharmacology and toxicology (USC School of Pharmacy) and professor of biochemistry (USC Keck School of Medicine).

Research Interests:

The anomalous regulation of apoptosis has been recognized as a pathological process that occurs in a variety of conditions comprising neurodegenerative diseases, autoimmune disorders, and various cancers. We are interested in elucidating the molecular mechanisms underlying cell signaling pathways inherent in mitochondrion-dependent apoptosis and with implications for neurodegenerative- and age-related disorders.

Ongoing research projects within these long-term goals are: (a) the study of the potential biological role of mitochondria as an important cellular target of pro-apoptotic JNK signalling involving modulation of Bcl-2 family members; (b) the regulation of mitochondrial functions by nitric oxide and the mitochondrial nitric oxide synthase and how they impinge on the cellular redox state; (c) analysis of the mitochondrial proteome for post-translational modifications caused by JNK activity and exposure to oxidative and nitrosative stress; (d) the analysis of the mechanism of actions of neuroprotective agents in terms of preserving mitochondrion functional integrity through activation of ligand-independent signaling pathways and universal transcription factors.

• 2013 Oxidative Stress and Disease Gordon Research Conference & Seminar
  NIH · R13AG044908 · Mar 15, 2013 – Feb 28, 2014 · Role: Principal Investigator
• XIIIth Biennial Meeting of the Society for Free Radical Research International
  NIH · R13CA124282 · Aug 1, 2006 – Jul 31, 2007 · Role: Principal Investigator
• Mitochondrial oxidative damage in dopaminergic cells
  NIH · R01ES011342 · Jul 11, 2001 – Jun 30, 2007 · Role: Principal Investigator
• Oxidative Stress, Mitochondrial Dysfunction and Aging
  NIH · R01AG016718 · Apr 1, 1999 – May 31, 2011 · Role: Principal Investigator
• BIOCHEMICAL TOXICOLOGY OF MYOGLOBIN OXIDATION STATES
  NIH · R01HL053467 · Jul 1, 1995 – Jun 30, 1999 · Role: Principal Investigator
• MODULATION OF QUINONE TOXICITY BY TWO-ELECTRON TRANSFERS
  NIH · R01ES005423 · Jul 1, 1990 – Jun 30, 1996 · Role: Principal Investigator

• Characterizing Kupffer Cell Production of CD5 Antigen-Like and Its Function on Regulating Migration of Natural Killer T Cells. Am J Pathol. 2025 10; 195(10):1839-1853.. View in PubMed
• Thiamine Deficiency and Neuroinflammation Are Important Contributors to Alcohol Use Disorder. Pathophysiology. 2025 Jul 04; 32(3).. View in PubMed
• Proinflammatory macrophages release CXCL5 to regulate T cell function and limit effects of αPD-1 in steatosis-driven liver cancer. JHEP Rep. 2025 Jun; 7(6):101385.. View in PubMed
• Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation. Front Nutr. 2023; 10:1201007.. View in PubMed
• Lester Packer: On His Life and His Legacy. Antioxid Redox Signal. 2023 04; 38(10-12):768-774.. View in PubMed
• Using the Cyclotide Scaffold for Targeting Biomolecular Interactions in Drug Development. Molecules. 2022 Sep 29; 27(19).. View in PubMed
• Modulation of hepatic amyloid precursor protein and lipoprotein receptor-related protein 1 by chronic alcohol intake: Potential link between liver steatosis and amyloid-β. Front Physiol. 2022; 13:930402.. View in PubMed
• Reprint of: Production of Superoxide Radicals and Hydrogen Peroxide by NADH- Ubiquinone Reductase and Ubiquinol-Cytochrome c Reductase from Beef-Heart Mitochondria. Arch Biochem Biophys. 2022 09 15; 726:109231.. View in PubMed
• On ‘Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria’ by Enrique Cadenas, Alberto Boveris, C. Ian Ragan and Andres O.M.Stoppani. Arch Biochem Biophys. 2022 09 15; 726:109214.. View in PubMed
• Redox Pioneer: Professor Valerian Kagan. Antioxid Redox Signal. 2022 05; 36(13-15):813-823.. View in PubMed
• Commentary on “Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria”. Arch Biochem Biophys. 2022 Mar 29; 721:109197.. View in PubMed
• Inhibition of Estrogen-Related Receptor α Blocks Liver Steatosis and Steatohepatitis and Attenuates Triglyceride Biosynthesis. Am J Pathol. 2021 07; 191(7):1240-1254.. View in PubMed
• Methionine restriction alleviates age-associated cognitive decline via fibroblast growth factor 21. Redox Biol. 2021 05; 41:101940.. View in PubMed
• High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis. Cell Metab. 2021 05 04; 33(5):923-938.e6.. View in PubMed
• The bioactivity of neuronal-derived nitric oxide in aging and neurodegeneration: Switching signaling to degeneration. Free Radic Biol Med. 2021 01; 162:500-513.. View in PubMed
• Dihydromyricetin improves mitochondrial outcomes in the liver of alcohol-fed mice via the AMPK/Sirt-1/PGC-1α signaling axis. Alcohol. 2021 03; 91:1-9.. View in PubMed
• Mitochondria as Target for Tumor Management of Hemangioendothelioma. Antioxid Redox Signal. 2021 01 10; 34(2):137-153.. View in PubMed
• Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat Commun. 2020 02 18; 11(1):855.. View in PubMed
• Treadmill exercise rescues mitochondrial function and motor behavior in the CAG140 knock-in mouse model of Huntington’s disease. Chem Biol Interact. 2020 Jan 05; 315:108907.. View in PubMed
• Brain metabolic and functional alterations in a liver-specific PTEN knockout mouse model. PLoS One. 2018; 13(9):e0204043.. View in PubMed
• The Oxygen Paradox, the French Paradox, and age-related diseases. Geroscience. 2017 12; 39(5-6):499-550.. View in PubMed
• Effects of Lipoic Acid on High-Fat Diet-Induced Alteration of Synaptic Plasticity and Brain Glucose Metabolism: A PET/CT and 13C-NMR Study. Sci Rep. 2017 07 14; 7(1):5391.. View in PubMed
• Editorial: The Metabolic-Inflammatory Axis in Brain Aging and Neurodegeneration. Front Aging Neurosci. 2017; 9:209.. View in PubMed
• Lipid quantitation and metabolomics data from vitamin E-deficient and -sufficient zebrafish embryos from 0 to 120 hours-post-fertilization. Data Brief. 2017 Apr; 11:432-441.. View in PubMed
• Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency. Free Radic Biol Med. 2017 03; 104:324-332.. View in PubMed
• Mitochondrial remodeling in the liver following chronic alcohol feeding to rats. Free Radic Biol Med. 2017 01; 102:100-110.. View in PubMed
• Introduction to Special Issue on Mitochondrial Redox Signaling in Health and Disease. Free Radic Biol Med. 2016 11; 100:1-4.. View in PubMed
• Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic Biol Med. 2016 11; 100:108-122.. View in PubMed
• Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling. J Clin Exp Pathol. 2016 Apr; 6(2).. View in PubMed
• Antioxidants, oxidants, and redox impacts on cell function – A tribute to Helmut Sies. Arch Biochem Biophys. 2016 Apr 01; 595:94-9.. View in PubMed
• Spatial Variations in Vitreous Oxygen Consumption. PLoS One. 2016; 11(3):e0149961.. View in PubMed
• Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration. J Alzheimers Dis. 2016; 50(1):133-48.. View in PubMed
• Tobacco Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration. J Alzheimers Dis. 2016; 50(2):373-86.. View in PubMed
• Cigarette Smoke-Induced Alterations in Frontal White Matter Lipid Profiles Demonstrated by MALDI-Imaging Mass Spectrometry: Relevance to Alzheimer’s Disease. J Alzheimers Dis. 2016; 51(1):151-63.. View in PubMed
• Mitochondrial function in ageing: coordination with signalling and transcriptional pathways. J Physiol. 2016 Apr 15; 594(8):2025-42.. View in PubMed
• High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS One. 2015; 10(5):e0128274.. View in PubMed
• Perimenopause as a neurological transition state. Nat Rev Endocrinol. 2015 Jul; 11(7):393-405.. View in PubMed
• The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity. Neurobiol Aging. 2015 Jul; 36(7):2282-2295.. View in PubMed
• Mitochondria: the cellular hub of the dynamic coordinated network. Antioxid Redox Signal. 2015 Apr 20; 22(12):961-4.. View in PubMed
• Preface. Methods Enzymol. 2015; 554:xv.. View in PubMed
• Polyphenols from green tea prevent antineuritogenic action of Nogo-A via 67-kDa laminin receptor and hydrogen peroxide. J Neurochem. 2015 Jan; 132(1):70-84.. View in PubMed
• Methods in Enzymology. Hydrogen sulfide in redox biology, part B. Preface. Methods Enzymol. 2015; 555:xv.. View in PubMed
• Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell. 2014 Dec; 13(6):1059-67.. View in PubMed
• Hypermetabolic state in the 7-month-old triple transgenic mouse model of Alzheimer’s disease and the effect of lipoic acid: a 13C-NMR study. J Cereb Blood Flow Metab. 2014 Nov; 34(11):1749-60.. View in PubMed
• Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells. Am J Respir Cell Mol Biol. 2014 Aug; 51(2):284-93.. View in PubMed
• Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide. Free Radic Biol Med. 2014 Aug; 73:421-9.. View in PubMed
• Respiratory substrates regulate S-nitrosylation of mitochondrial proteins through a thiol-dependent pathway. Chem Res Toxicol. 2014 May 19; 27(5):794-804.. View in PubMed
• Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells. Aging Cell. 2014 04; 13(2):367-78.. View in PubMed
• Green tea catechins potentiate the neuritogenic action of brain-derived neurotrophic factor: role of 67-kDa laminin receptor and hydrogen peroxide. Biochem Biophys Res Commun. 2014 Feb 28; 445(1):218-24.. View in PubMed
• Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer’s disease: a 13C NMR study. J Cereb Blood Flow Metab. 2014 Feb; 34(2):288-96.. View in PubMed
• Metabolic shift in lung alveolar cell mitochondria following acrolein exposure. Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15; 305(10):L764-73.. View in PubMed
• Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway. Aging Cell. 2013 Dec; 12(6):1021-31.. View in PubMed
• Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease. PLoS One. 2013; 8(7):e69830.. View in PubMed
• Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling regulates mitochondrial biogenesis and respiration via estrogen-related receptor α (ERRα). J Biol Chem. 2013 Aug 30; 288(35):25007-25024.. View in PubMed
• Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling. Biochem Soc Trans. 2013 Feb 01; 41(1):101-5.. View in PubMed
• PI3K/AKT signaling regulates bioenergetics in immortalized hepatocytes. Free Radic Biol Med. 2013 Jul; 60:29-40.. View in PubMed
• H2O2 delivery to cells: steady-state versus bolus addition. Methods Enzymol. 2013; 526:159-73.. View in PubMed
• The cellular steady-state of H2O2: latency concepts and gradients. Methods Enzymol. 2013; 527:3-19.. View in PubMed
• Methods in Enzymology. Hydrogen peroxide and cell signaling, part C. Preface. Methods Enzymol. 2013; 528:xv.. View in PubMed
• Methods in Enzymology. Hydrogen peroxide and cell signaling, part B. Preface. Methods Enzymol. 2013; 527:xv.. View in PubMed
• Preface. Hydrogen peroxide and cell signaling, part A. Methods Enzymol. 2013; 526:xv.. View in PubMed
• Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations. J Biol Chem. 2012 Dec 07; 287(50):42165-79.. View in PubMed
• Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs. Am J Physiol Lung Cell Mol Physiol. 2012 Nov 15; 303(10):L889-98.. View in PubMed
• Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration. Antioxid Redox Signal. 2014 Jan 10; 20(2):353-71.. View in PubMed
• Mitochondrial thiols in the regulation of cell death pathways. Antioxid Redox Signal. 2012 Dec 15; 17(12):1714-27.. View in PubMed
• Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells. J Biol Chem. 2012 Apr 20; 287(17):14088-98.. View in PubMed
• Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. PLoS One. 2012; 7(2):e31267.. View in PubMed
• Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function. J Neuroendocrinol. 2012 Jan; 24(1):236-48.. View in PubMed
• Silencing of nicotinamide nucleotide transhydrogenase impairs cellular redox homeostasis and energy metabolism in PC12 cells. Biochim Biophys Acta. 2012 Mar; 1817(3):401-9.. View in PubMed
• Shift in brain metabolism in late onset Alzheimer’s disease: implications for biomarkers and therapeutic interventions. Mol Aspects Med. 2011 Aug; 32(4-6):247-57.. View in PubMed
• 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PLoS One. 2011; 6(7):e21788.. View in PubMed
• Evidence for a pathway that facilitates nitric oxide diffusion in the brain. Neurochem Int. 2011 Aug; 59(1):90-6.. View in PubMed
• Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid. Neurobiol Aging. 2012 Aug; 33(8):1507-21.. View in PubMed
• Melatonin and steroid hormones activate intermembrane Cu,Zn-superoxide dismutase by means of mitochondrial cytochrome P450. Free Radic Biol Med. 2011 Jun 01; 50(11):1575-81.. View in PubMed
• Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr. 2011 Jan; 48(1):26-32.. View in PubMed
• Medroxyprogesterone acetate antagonizes estrogen up-regulation of brain mitochondrial function. Endocrinology. 2011 Feb; 152(2):556-67.. View in PubMed
• Estrogen protection against mitochondrial toxin-induced cell death in hippocampal neurons: antagonism by progesterone. Brain Res. 2011 Mar 16; 1379:2-10.. View in PubMed
• Protein post-translational modifications in cell signalling and disease. Free Radic Res. 2011 Jan; 45(1):1-2.. View in PubMed
• Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J Biol Chem. 2010 Dec 17; 285(51):39646-54.. View in PubMed
• Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence. Biochim Biophys Acta. 2010 Oct; 1800(10):1121-6.. View in PubMed
• Role of nitric oxide-mediated glutathionylation in neuronal function: potential regulation of energy utilization. Biochem J. 2010 Apr 28; 428(1):85-93.. View in PubMed
• In vivo modulation of nitric oxide concentration dynamics upon glutamatergic neuronal activation in the hippocampus. Hippocampus. 2011 Jun; 21(6):622-30.. View in PubMed
• Dynamic and interacting profiles of *NO and O2 in rat hippocampal slices. Free Radic Biol Med. 2010 Apr 15; 48(8):1044-50.. View in PubMed
• Determination of GSH, GSSG, and GSNO using HPLC with electrochemical detection. Methods Enzymol. 2010; 473:137-47.. View in PubMed
• Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression. PLoS One. 2009 Oct 21; 4(10):e7523.. View in PubMed
• Mitochondrial medicine and therapeutics, Part II. Preface. Adv Drug Deliv Rev. 2009 Nov 30; 61(14):1233.. View in PubMed
• The energy-redox axis in aging and age-related neurodegeneration. Adv Drug Deliv Rev. 2009 Nov 30; 61(14):1283-98.. View in PubMed
• Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production. Free Radic Res. 2009 May; 43(5):431-9.. View in PubMed
• Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. FEBS Lett. 2009 Apr 02; 583(7):1132-40.. View in PubMed
• Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood. 2009 Jun 04; 113(23):5927-37.. View in PubMed
• Compromised proteasome degradation elevates neuronal nitric oxide synthase levels and induces apoptotic cell death. Arch Biochem Biophys. 2008 Oct 15; 478(2):181-6.. View in PubMed
• Mitochondrial medicine and mitochondrion-based therapeutics. Adv Drug Deliv Rev. 2008 Oct-Nov; 60(13-14):1437-8.. View in PubMed
• Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria. PLoS One. 2008 Jun 11; 3(6):e2379.. View in PubMed
• [Validation of the Spanish version of the QOLIE-10 quality of life in epilepsy questionnaire]. Neurologia. 2008 Apr; 23(3):157-67.. View in PubMed
• Progesterone and estrogen regulate oxidative metabolism in brain mitochondria. Endocrinology. 2008 Jun; 149(6):3167-75.. View in PubMed
• Hippocampal mitochondrial dysfunction in rat aging. Am J Physiol Regul Integr Comp Physiol. 2008 Feb; 294(2):R501-9.. View in PubMed
• c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. J Neurochem. 2008 Jan; 104(2):325-35.. View in PubMed
• Inhibition of cellular proliferation by the genistein metabolite 5,7,3′,4′-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathway. Arch Biochem Biophys. 2007 Dec 15; 468(2):159-66.. View in PubMed
• On the biologic role of the reaction of NO with oxidized cytochrome c oxidase. Antioxid Redox Signal. 2007 Oct; 9(10):1569-79.. View in PubMed
• Oxidants and antioxidants revisited. New concepts of oxidative stress. Free Radic Res. 2007 Sep; 41(9):951-2.. View in PubMed

• Kaplowitz, Neil
• Papadopoulos, Vassilios
• Cohen, Pinchas
• Longo, Valter
• Thompson, Paul
• Finch, Caleb