Ajit S Divakaruni
Assistant Professor, Molecular and Medical Pharmacology, University of California Los Angeles
adivakaruni@mednet.ucla.edu
Affiliations
Member, I3T Theme, Molecular Pharmacology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Biography
Our laboratory has broad interest in mitochondrial metabolism and bioenergetics, with a particular emphasis on targeting mitochondrial inner membrane transporters to treat metabolic and neurodegenerative disease. Facilitated transport of metabolites, co-factors, and ions across the mitochondrial inner membrane can regulate a range of physiological processes including those as varied as thermogenesis, maintenance of euglycemia, and synaptic neurotransmission. Methodologically, we integrate bioenergetic measurements with metabolomics and stable isotope tracing to characterize cellular energy metabolism. We are also actively developing new assays, protocols, and data interpretation roadmaps to help make these measurements accessible to non-specialists interested in metabolism and mitochondrial function.
Publications
- Fernandez-Del-Rio L, Beninc? C, Villalobos F, Shu C, Stiles L, Liesa M, Divakaruni AS, Acin-Perez R, Shirihai OS. A novel approach to measure complex V ATP hydrolysis in frozen cell lysates and tissue homogenates.. Life science alliance, 2023.
- Ngo J, Choi DW, Stanley IA, Stiles L, Molina AJA, Chen PH, Lako A, Sung ICH, Goswami R, Kim MY, Miller N, Baghdasarian S, Kim-Vasquez D, Jones AE, Roach B, Gutierrez V, Erion K, Divakaruni AS, Liesa M, Danial NN, Shirihai OS. Mitochondrial morphology controls fatty acid utilization by changing CPT1 sensitivity to malonyl-CoA.. The EMBO journal, 2023.
- Yan T, Julio AR, Villanueva M, Jones AE, Ball AAB, Boatner LM, Turmon AC, Yen SL, Desai HS, Divakaruni AS, Backus KM. Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.. bioRxiv : the preprint server for biology, 2023.
- Hazim RA, Paniagua AE, Tang L, Yang K, Kim KKO, Stiles L, Divakaruni AS, Williams DS. Correction: Vitamin B3, nicotinamide, enhances mitochondrial metabolism to promote differentiation of the retinal pigment epithelium.. The Journal of biological chemistry, 2022.
- Divakaruni AS, Jastroch M. A practical guide for the analysis, standardization and interpretation of oxygen consumption measurements.. Nature metabolism, 2022.
- Hazim RA, Paniagua AE, Tang L, Yang K, Kim KKO, Stiles L, Divakaruni AS, Williams DS. Vitamin B3, nicotinamide, enhances mitochondrial metabolism to promote differentiation of the retinal pigment epithelium.. The Journal of biological chemistry, 2022.
- Cho NS, Hagiwara A, Yao J, Nathanson DA, Prins RM, Wang C, Raymond C, Desousa BR, Divakaruni A, Morrow DH, Nghiemphu PL, Lai A, Liau LM, Everson RG, Salamon N, Pope WB, Cloughesy TF, Ellingson BM. Amine-weighted chemical exchange saturation transfer magnetic resonance imaging in brain tumors.. NMR in biomedicine, 2022.
- Meriwether D, Jones AE, Ashby JW, Solorzano-Vargas RS, Dorreh N, Noori S, Grijalva V, Ball AB, Semis M, Divakaruni AS, Mack JJ, Herschman HR, Martin MG, Fogelman AM, Reddy ST. Macrophage COX2 Mediates Efferocytosis, Resolution Reprogramming, and Intestinal Epithelial Repair.. Cellular and molecular gastroenterology and hepatology, 2022.
- Hagiwara A, Yao J, Raymond C, Cho NS, Everson R, Patel K, Morrow DH, Desousa BR, Mareninov S, Chun S, Nathanson DA, Yong WH, Andrei G, Divakaruni AS, Salamon N, Pope WB, Nghiemphu PL, Liau LM, Cloughesy TF, Ellingson BM. "Aerobic glycolytic imaging" of human gliomas using combined pH-, oxygen-, and perfusion-weighted magnetic resonance imaging.. NeuroImage. Clinical, 2021.
- Yang K, Doan MT, Stiles L, Divakaruni AS. Measuring CPT-1-mediated respiration in permeabilized cells and isolated mitochondria.. STAR protocols, 2021.
- Jones AE, Arias NJ, Acevedo A, Reddy ST, Divakaruni AS, Meriwether D. A Single LC-MS/MS Analysis to Quantify CoA Biosynthetic Intermediates and Short-Chain Acyl CoAs.. Metabolites, 2021.
- Tucci J, Chen T, Margulis K, Orgel E, Paszkiewicz RL, Cohen MD, Oberley MJ, Wahhab R, Jones AE, Divakaruni AS, Hsu CC, Noll SE, Sheng X, Zare RN, Mittelman SD. Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells.. Frontiers in oncology, 2021.
- Jacques V, Bolze S, Hallakou-Bozec S, Czarnik AW, Divakaruni AS, Fouqueray P, Murphy AN, Van der Ploeg LHT, DeWitt S. Deuterium-Stabilized (R)-Pioglitazone (PXL065) Is Responsible for Pioglitazone Efficacy in NASH yet Exhibits Little to No PPARγ Activity.. Hepatology communications, 2021.
- Veliova M, Ferreira CM, Benador IY, Jones AE, Mahdaviani K, Brownstein AJ, Desousa BR, Acín-Pérez R, Petcherski A, Assali EA, Stiles L, Divakaruni AS, Prentki M, Corkey BE, Liesa M, Oliveira MF, Shirihai OS. Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling.. EMBO reports, 2020.
- Jones AE, Sheng L, Acevedo A, Veliova M, Shirihai OS, Stiles L, Divakaruni AS. Forces, fluxes, and fuels: tracking mitochondrial metabolism by integrating measurements of membrane potential, respiration, and metabolites.. American journal of physiology. Cell physiology, 2020.
- Chella Krishnan K, Floyd RR, Sabir S, Jayasekera DW, Leon-Mimila PV, Jones AE, Cortez AA, Shravah V, Péterfy M, Stiles L, Canizales-Quinteros S, Divakaruni AS, Huertas-Vazquez A, Lusis AJ. Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner.. Cellular and molecular gastroenterology and hepatology, 2020.
- Sperry J, Condro MC, Guo L, Braas D, Vanderveer-Harris N, Kim KKO, Pope WB, Divakaruni AS, Lai A, Christofk H, Castro MG, Lowenstein PR, Le Belle JE, Kornblum HI. Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy.. iScience, 2020.
- Hsieh WY, Zhou QD, York AG, Williams KJ, Scumpia PO, Kronenberger EB, Hoi XP, Su B, Chi X, Bui VL, Khialeeva E, Kaplan A, Son YM, Divakaruni AS, Sun J, Smale ST, Flavell RA, Bensinger SJ. Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome.. Cell metabolism, 2020.
- Acin-Perez R, Benador IY, Petcherski A, Veliova M, Benavides GA, Lagarrigue S, Caudal A, Vergnes L, Murphy AN, Karamanlidis G, Tian R, Reue K, Wanagat J, Sacks H, Amati F, Darley-Usmar VM, Liesa M, Divakaruni AS, Stiles L, Shirihai OS. A novel approach to measure mitochondrial respiration in frozen biological samples.. The EMBO journal, 2020.
- Jones AE, Divakaruni AS. Macrophage activation as an archetype of mitochondrial repurposing.. Molecular aspects of medicine, 2020.
- Cao DY, Spivia WR, Veiras LC, Khan Z, Peng Z, Jones AE, Bernstein EA, Saito S, Okwan-Duodu D, Parker SJ, Giani JF, Divakaruni AS, Van Eyk JE, Bernstein KE. ACE overexpression in myeloid cells increases oxidative metabolism and cellular ATP.. The Journal of biological chemistry, 2019.
- Cordes T, Lucas A, Divakaruni AS, Murphy AN, Cabrales P, Metallo CM. Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury.. Molecular metabolism, 2019.
- Divakaruni AS, Murphy AN. Do Two Mitochondrial Wrongs Help Make Cells Right?. Trends in molecular medicine, 2019.
- Woodall BP, Orogo AM, Najor RH, Cortez MQ, Moreno ER, Wang H, Divakaruni AS, Murphy AN, Gustafsson ÅB. Parkin does not prevent accelerated cardiac aging in mitochondrial DNA mutator mice.. JCI insight, 2019.
- Wortham M, Benthuysen JR, Wallace M, Savas JN, Mulas F, Divakaruni AS, Liu F, Albert V, Taylor BL, Sui Y, Saez E, Murphy AN, Yates JR, Metallo CM, Sander M. Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function.. Cell reports, 2018.
- Sessions AO, Min P, Cordes T, Weickert BJ, Divakaruni AS, Murphy AN, Metallo CM, Engler AJ. Preserved cardiac function by vinculin enhances glucose oxidation and extends health- and life-span.. APL bioengineering, 2018.
- Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R, Ma EH, Samborska B, Hsieh WY, Wong AH, Stüve P, Arnold-Schrauf C, Guderian M, Lochner M, Rampertaap S, Romito K, Monsale J, Brönstrup M, Bensinger SJ, Murphy AN, McGuire PJ, Jones RG, Sparwasser T, Berod L. Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation.. Cell metabolism, 2018.
- Divakaruni AS, Hsieh WY, Minarrieta L, Duong TN, Kim KKO, Desousa BR, Andreyev AY, Bowman CE, Caradonna K, Dranka BP, Ferrick DA, Liesa M, Stiles L, Rogers GW, Braas D, Ciaraldi TP, Wolfgang MJ, Sparwasser T, Berod L, Bensinger SJ, Murphy AN. Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis.. Cell metabolism, 2018.
- Divakaruni AS, Andreyev AY, Rogers GW, Murphy AN. In situ measurements of mitochondrial matrix enzyme activities using plasma and mitochondrial membrane permeabilization agents.. Analytical biochemistry, 2017.
- Hashem SI, Murphy AN, Divakaruni AS, Klos ML, Nelson BC, Gault EC, Rowland TJ, Perry CN, Gu Y, Dalton ND, Bradford WH, Devaney EJ, Peterson KL, Jones KL, Taylor MRG, Chen J, Chi NC, Adler ED. Impaired mitophagy facilitates mitochondrial damage in Danon disease.. Journal of molecular and cellular cardiology, 2017.
- Divakaruni AS, Wallace M, Buren C, Martyniuk K, Andreyev AY, Li E, Fields JA, Cordes T, Reynolds IJ, Bloodgood BL, Raymond LA, Metallo CM, Murphy AN. Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.. The Journal of cell biology, 2017.
- Parker SJ, Svensson RU, Divakaruni AS, Lefebvre AE, Murphy AN, Shaw RJ, Metallo CM. LKB1 promotes metabolic flexibility in response to energy stress.. Metabolic engineering, 2016.
- Zhang H, Badur MG, Divakaruni AS, Parker SJ, Jäger C, Hiller K, Murphy AN, Metallo CM. Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions.. Cell reports, 2016.
- Garcia-Carbonell R, Divakaruni AS, Lodi A, Vicente-Suarez I, Saha A, Cheroutre H, Boss GR, Tiziani S, Murphy AN, Guma M. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes.. Arthritis & rheumatology (Hoboken, N.J.), 2016.
- Cordes T, Wallace M, Michelucci A, Divakaruni AS, Sapcariu SC, Sousa C, Koseki H, Cabrales P, Murphy AN, Hiller K, Metallo CM. Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels.. The Journal of biological chemistry, 2016.
- Ding B, Parmigiani A, Divakaruni AS, Archer K, Murphy AN, Budanov AV. Sestrin2 is induced by glucose starvation via the unfolded protein response and protects cells from non-canonical necroptotic cell death.. Scientific reports, 2016.
- Fields JA, Serger E, Campos S, Divakaruni AS, Kim C, Smith K, Trejo M, Adame A, Spencer B, Rockenstein E, Murphy AN, Ellis RJ, Letendre S, Grant I, Masliah E. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-associated neurocognitive disorders.. Neurobiology of disease, 2015.
- Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP, Metallo CM. Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis.. Nature chemical biology, 2015.
- Giacco F, Du X, Carratú A, Gerfen GJ, D'Apolito M, Giardino I, Rasola A, Marin O, Divakaruni AS, Murphy AN, Shah MS, Brownlee M. GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.. Diabetes, 2015.
- Wilderman A, Guo Y, Divakaruni AS, Perkins G, Zhang L, Murphy AN, Taylor SS, Insel PA. Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of Mitochondria by cAMP and Protein Kinase A.. The Journal of biological chemistry, 2015.
- Westenbrink BD, Ling H, Divakaruni AS, Gray CB, Zambon AC, Dalton ND, Peterson KL, Gu Y, Matkovich SJ, Murphy AN, Miyamoto S, Dorn GW, Heller Brown J. Mitochondrial reprogramming induced by CaMKIIδ mediates hypertrophy decompensation.. Circulation research, 2015.
- Vacanti NM, Divakaruni AS, Green CR, Parker SJ, Henry RR, Ciaraldi TP, Murphy AN, Metallo CM. Regulation of substrate utilization by the mitochondrial pyruvate carrier.. Molecular cell, 2014.
- Rogers GW, Nadanaciva S, Swiss R, Divakaruni AS, Will Y. Assessment of fatty acid beta oxidation in cells and isolated mitochondria.. Current protocols in toxicology, 2014.
- Divakaruni AS, Rogers GW, Murphy AN. Measuring Mitochondrial Function in Permeabilized Cells Using the Seahorse XF Analyzer or a Clark-Type Oxygen Electrode.. Current protocols in toxicology, 2014.
- Yamazaki KG, Andreyev AY, Ortiz-Vilchis P, Petrosyan S, Divakaruni AS, Wiley SE, De La Fuente C, Perkins G, Ceballos G, Villarreal F, Murphy AN. Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function.. International journal of cardiology, 2014.
- Grassian AR, Parker SJ, Davidson SM, Divakaruni AS, Green CR, Zhang X, Slocum KL, Pu M, Lin F, Vickers C, Joud-Caldwell C, Chung F, Yin H, Handly ED, Straub C, Growney JD, Vander Heiden MG, Murphy AN, Pagliarini R, Metallo CM. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.. Cancer research, 2014.
- Divakaruni AS, Paradyse A, Ferrick DA, Murphy AN, Jastroch M. Analysis and interpretation of microplate-based oxygen consumption and pH data.. Methods in enzymology, 2014.
- Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomsig JL, Okabe K, Lo RH, Cameron Coleman G, Columbus L, Yan Z, Saucerman JJ, Smith JS, Holmes JW, Lynch KR, Ravichandran KS, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, Hoehn KL. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane.. Molecular metabolism, 2013.
- Wiley SE, Andreyev AY, Divakaruni AS, Karisch R, Perkins G, Wall EA, van der Geer P, Chen YF, Tsai TF, Simon MI, Neel BG, Dixon JE, Murphy AN. Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.. EMBO molecular medicine, 2013.
- Colca JR, McDonald WG, Cavey GS, Cole SL, Holewa DD, Brightwell-Conrad AS, Wolfe CL, Wheeler JS, Coulter KR, Kilkuskie PM, Gracheva E, Korshunova Y, Trusgnich M, Karr R, Wiley SE, Divakaruni AS, Murphy AN, Vigueira PA, Finck BN, Kletzien RF. Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)--relationship to newly identified mitochondrial pyruvate carrier proteins.. PloS one, 2013.
- Divakaruni AS, Wiley SE, Rogers GW, Andreyev AY, Petrosyan S, Loviscach M, Wall EA, Yadava N, Heuck AP, Ferrick DA, Henry RR, McDonald WG, Colca JR, Simon MI, Ciaraldi TP, Murphy AN. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
- Divakaruni AS, Humphrey DM, Brand MD. Fatty acids change the conformation of uncoupling protein 1 (UCP1).. The Journal of biological chemistry, 2012.
- Divakaruni AS, Murphy AN. Cell biology. A mitochondrial mystery, solved.. Science (New York, N.Y.), 2012.
- Divakaruni AS, Brand MD. The regulation and physiology of mitochondrial proton leak.. Physiology (Bethesda, Md.), 2011.
- Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD. Mitochondrial uncoupling and lifespan.. Mechanisms of ageing and development, 2010.
- Azzu V, Jastroch M, Divakaruni AS, Brand MD. The regulation and turnover of mitochondrial uncoupling proteins.. Biochimica et biophysica acta, 2010.
- Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD. Mitochondrial proton and electron leaks.. Essays in biochemistry, 2010.
- Gerencser AA, Mark KA, Hubbard AE, Divakaruni AS, Mehrabian Z, Nicholls DG, Polster BM. Real-time visualization of cytoplasmic calpain activation and calcium deregulation in acute glutamate excitotoxicity.. Journal of neurochemistry, 2009.