The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells
Open accessAbstract
Mitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The availability of NAD+ as an electron acceptor enables aspartate synthesis through aspartate aminotransferase and rescues the proliferation of cultured cells with dysfunctions or inhibition of the electron transport system [16,17].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Despite the prevalence of glycolysis, mitochondrial respiration remains important in proliferating cells, allowing the production of biosynthetic precursors and the generation of electron acceptors that enable aspartate synthesis, for example [9,16,17].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [17]
In the citing paper
“Genetic or epigenetic silencing of ASS1 expression provides an advantage to tumor cells by allowing them to preserve cellular aspartate (Rabinovich et al., 2015), a poorly transported nutrient that can be a critical output of the TCA cycle to support de novo nucleotide synthesis and cell proliferation (Birsoy et al., 2015; Sullivan et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Sullivan et al., 2015
In the citing paper
“However, mitochondrial ATP production appears dispensable for many proliferating cells (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Sullivan et al., 2015
In the citing paper
“Instead, respiration serves an alternative anabolic role for proliferating cells by regenerating the oxidized form of nicotinamide adenine dinucleotide (NAD+) from the reduced form (NADH) (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Sullivan et al., 2015
In the citing paper
“For example, eliminating environmental serine, limiting aspartate synthesis via mitochondrial inhibition, and ablating the mitochondrial folate pathway impairs purine biosynthesis (Ducker et al., 2016; Labuschagne et al., 2014; Sullivan et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Sullivan et al., 2015
In the citing paper
“Additionally, glutamine-derived aspartate plays a crucial role in hypoxic environments or environments with electron transport chain (ETC) impairment28.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [28]
In the citing paper
“Aspartate, which is derived from the transamination of glutamine to form glutamate, participates in pyrimidine and purine biosynthesis28.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [28]
In the citing paper
“Upon ETC dysfunction, the cytosolic steps of the malate–aspartate shuttle can reverse to produce, rather than consume, cytosolic aspartate (42, 43).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [43]
In the citing paper
“Aspartate is used to support protein and nucleotide synthesis in proliferating cells and sustains proliferation in the face of OXPHOS impairment (214).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [214]
In the citing paper
“Time-restricted feeding restores both cycling of metabolic regulators such as cAMP response element-binding protein, mTOR and AMPK, and circadian clock gene expression (214).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [214]
In the citing paper
“In fact, aspartate biosynthesis has recently been shown to be critically dependent upon a cell’s ability to conduct oxidative phosphorylation (Birsoy et al., 2015; Sullivan et al., 2015).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Sullivan et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931
Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism
MITCHELL, P. (1961) · Nature · doi:10.1038/191144a0 · Cited by 4,704
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
Assessing mitochondrial dysfunction in cells
Brand, M. D., & Nicholls, D. G. (2011) · Biochemical Journal · doi:10.1042/bj20110162 · Cited by 2,436
Wallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 1,001
Metabolic Remodeling Promotes Cardiac Hypertrophy by Directing Glucose to Aspartate Biosynthesis
Ritterhoff, J., Young, S., Villet, O. M., Shao, D., Neto, F. C., Bettcher, L., Hsu, Y. A., Kolwicz, S. C., Raftery, D., & Tian, R. (2019) · Circulation Research · doi:10.1161/circresaha.119.315483 · Cited by 229
Metformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers
Liu, X., Romero, I. L., Litchfield, L. M., Lengyel, E. R., & Locasale, J. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.005 · Cited by 229
Gaude, E., Schmidt, C., Gammage, P. A., Dugourd, A. J. F., Blacker, T. S., Peak‐Chew, S., Sáez-Rodríguez, J., O'Neill, J. S., Szabadkai, G., Minczuk, M. A., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.034 · Cited by 235
Reid, M. A., Allen, A. E., Liu, S., Liberti, M. V., Liu, P., Liu, X., Dai, Z., Gao, X., Wang, Q., Liu, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07868-6 · Cited by 240
Cell Clustering Promotes a Metabolic Switch that Supports Metastatic Colonization
Labuschagne, C. F., Cheung, E. C., Blagih, J., Domart, M., & Vousden, K. H. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.014 · Cited by 225
l-Aspartate: An Essential Metabolite for Plant Growth and Stress Acclimation
Han, M., Zhang, C., Suglo, P., Sun, S., Wang, M., & Su, T. (2021) · Molecules · doi:10.3390/molecules26071887 · Cited by 223
Metabolic reprogramming in prostate cancer
Ahmad, F., Cherukuri, M. K., & Choyke, P. L. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01435-5 · Cited by 238
mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells
Pusapati, R. V., Daemen, A., Wilson, C., Sandoval, W. N., Gao, M., Haley, B., Baudy, A. R., Hatzivassiliou, G., Evangelista, M., & Settleman, J. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.02.018 · Cited by 221
The Warburg metabolism fuels tumor metastasis
Lu, J. (2019) · Cancer and Metastasis Reviews · doi:10.1007/s10555-019-09794-5 · Cited by 221
Cancer metabolism in space and time: Beyond the Warburg effect
Danhier, P., Bański, P., Payen, V. L., Grasso, D., Ippolito, L., Sonveaux, P., & Porporato, P. E. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.02.001 · Cited by 230
Yao, C.-H., Liu, G., Wang, R., Moon, S. H., Gross, R. W., & Patti, G. J. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2003782 · Cited by 222
The Diverse Functions of Non-Essential Amino Acids in Cancer
Choi, B.-H., & Coloff, J. L. (2019) · Cancers · doi:10.3390/cancers11050675 · Cited by 213
Serine Catabolism Feeds NADH when Respiration Is Impaired
Yang, L., García‐Cañaveras, J. C., Chen, Z., Wang, L., Liang, L., Jang, C., Mayr, J. A., Zhang, Z., Ghergurovich, J. M., Zhan, L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.02.017 · Cited by 216
An expanded universe of cancer targets
Hahn, W. C., Bader, J. S., Braun, T. P., Califano, A., Clemons, P. A., Druker, B. J., Ewald, A. J., Fu, H., Jagu, S., Kemp, C. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.020 · Cited by 213
Chen, Q., Kirk, K., Shurubor, Y. I., Zhao, D., Arreguin, A. J., Shahi, I., Valsecchi, F., Primiano, G., Calder, E. L., Carelli, V., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.002 · Cited by 210
Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells
Chen, P.-H., Cai, L., Huffman, K. E., Yang, C., Kim, J., Faubert, B., Boroughs, L. K., Ko, B., Sudderth, J., McMillan, E. A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.028 · Cited by 209
Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting
Alkan, H. F., Walter, K. E., Luengo, A., Madreiter‐Sokolowski, C. T., Stryeck, S., Lau, A. N., Zoughbi, W. A., Lewis, C. A., Thomas, C. J., Höefler, G., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.021 · Cited by 205
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Vernieri, C., Casola, S., Foiani, M., Pietrantonio, F., de Braud, F., & Longo, V. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0615 · Cited by 202
Nucleotide imbalance decouples cell growth from cell proliferation
Diehl, F. F., Miettinen, T. P., Elbashir, R., Nabel, C. S., Darnell, A. M., Do, B. T., Manalis, S. R., Lewis, C. A., & Heiden, M. G. V. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00965-1 · Cited by 218
Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis
Diebold, L. P., Gil, H. J., Gao, P., Martinez, C. A., Weinberg, S. E., & Chandel, N. S. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0011-x · Cited by 200
From OCR and ECAR to energy: Perspectives on the design and interpretation of bioenergetics studies
Schmidt, C. A., Fisher‐Wellman, K. H., & Neufer, P. D. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101140 · Cited by 206
Proline biosynthesis is a vent for TGFβ‐induced mitochondrial redox stress
Schwörer, S., Berisa, M., Violante, S., Qin, W., Zhu, J., Hendrickson, R. C., Cross, J. R., & Thompson, C. B. (2020) · The EMBO Journal · doi:10.15252/embj.2019103334 · Cited by 193
Minton, D. R., Nam, M., McLaughlin, D. J., Shin, J., Bayraktar, E. C., Alvarez, S., Sviderskiy, V. O., Papagiannakopoulos, T. Y., Sabatini, D. M., Birsoy, K., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.024 · Cited by 192
Oxidative Metabolism Drives Immortalization of Neural Stem Cells during Tumorigenesis
Bonnay, F., Veloso, A., Steinmann, V., Köcher, T., Abdusselamoglu, M. D., Bajaj, S., Rivelles, E., Landskron, L., Esterbauer, H., Zinzen, R. P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.039 · Cited by 191
Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells
Vandekeere, S., Dubois, C., Kalucka, J. M., Sullivan, M. R., García‐Caballero, M., Goveia, J., Chen, R., Diehl, F. F., Bar-Lev, L., Souffreau, J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.009 · Cited by 191
de Boer, R. A., Hulot, J., Tocchetti, C. G., Aboumsallem, J. P., Ameri, P., Anker, S. D., Bauersachs, J. K., Bertero, E., Coats, A. J. S., Čelutkienė, J., et al. (2020) · European Journal of Heart Failure · doi:10.1002/ejhf.2029 · Cited by 188
Vogel, A. D., Upadhya, R., & Shetty, A. K. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.026 · Cited by 186
The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma
Momcilovic, M., Bailey, S. T., Lee, J. T., Fishbein, M. C., Braas, D., Go, J. L., Graeber, T. G., Parlati, F., Demo, S. D., Li, R., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.04.002 · Cited by 187
Saturation of the mitochondrial NADH shuttles drives aerobic glycolysis in proliferating cells
Wang, Y., Stancliffe, E., Fowle-Grider, R., Wang, R., Wang, C., Schwaiger-Haber, M., Shriver, L. P., & Patti, G. J. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.07.007 · Cited by 180
Metabolic Plasticity in Chemotherapy Resistance
Desbats, M. A., Giacomini, I., Prayer‐Galetti, T., & Montopoli, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00281 · Cited by 190
Selective alanine transporter utilization creates a targetable metabolic niche in pancreatic cancer
Parker, S. J., Amendola, C. R., Hollinshead, K. E. R., Yu, Q., Yamamoto, K., Encarnación-Rosado, J., Rose, R. E., LaRue, M. M., Sohn, A. S. W., Biancur, D. E., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0959 · Cited by 175
MYC-Driven Small-Cell Lung Cancer is Metabolically Distinct and Vulnerable to Arginine Depletion
Chalishazar, M. D., Wait, S. J., Huang, F., Ireland, A. S., Mukhopadhyay, A., Lee, Y., Schuman, S. S., Guthrie, M. R., Berrett, K. C., Vahrenkamp, J. M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4140 · Cited by 175
Metabolic analysis as a driver for discovery, diagnosis, and therapy
DeBerardinis, R. J., & Keshari, K. R. (2022) · Cell · doi:10.1016/j.cell.2022.06.029 · Cited by 177
Cancer cell metabolism and mitochondria: Nutrient plasticity for TCA cycle fueling
Corbet, C., & Féron, O. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.01.002 · Cited by 174
Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier
Bensard, C., Wisidagama, D. R., Olson, K. A., Berg, J. A., Krah, N. M., Schell, J. C., Nowinski, S. M., Fogarty, S., Bott, A. J., Wei, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.002 · Cited by 170
Wang, Y.-Q., Wang, H.-L., Xu, J., Tan, J., Fu, L., Wang, J., Zou, T., Sun, D., Gao, Q., Chen, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02951-4 · Cited by 169
Metabolic rewiring in melanoma
Ratnikov, B. I., Scott, D. A., Osterman, A. L., Smith, J. W., & Ronai, Z. A. (2016) · Oncogene · doi:10.1038/onc.2016.198 · Cited by 176
Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer
Boukalová, Š., Hubáčková, S., Milošević, M., Ezrova, Z., Neužil, J., & Rohlena, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165759 · Cited by 167
Zhu, L., Zhu, X., & Wu, Y. (2022) · Biomolecules · doi:10.3390/biom12040580 · Cited by 167
Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction
Cheng, C.-T., Qi, Y., Wang, Y.-C., Chi, K. K., Chung, Y., Ouyang, C., Chen, Y.-R., Oh, M. E., Sheng, X., Tang, Y., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0178-4 · Cited by 164
Mitochondrial activity in T cells
Desdín-Micó, G., Soto‐Heredero, G., & Mittelbrunn, M. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.10.006 · Cited by 171
Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?
Xu, Y., Xue, D., Bankhead, A., & Neamati, N. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01013 · Cited by 173
Kremer, J. C., Prudner, B. C., Lange, S. E. S., Bean, G. R., Schultze, M., Brashears, C. B., Radyk, M. D., Redlich, N. J., Tzeng, S., Kami, K., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.077 · Cited by 169
Nitrogen Metabolism in Cancer and Immunity
Kurmi, K., & Haigis, M. C. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.02.005 · Cited by 167
Diehl, F. F., Lewis, C. A., Fiske, B. P., & Vander Heiden, M. G. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0108-x · Cited by 159
Targeting MTHFD2 in acute myeloid leukemia
Pikman, Y., Puissant, A., Alexe, G., Furman, A. A., Chen, L. M., Frumm, S. M., Ross, L. S., Fenouille, N., Bassil, C. F., Lewis, C. A., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151574 · Cited by 157
Targeting the Warburg effect via LDHA inhibition engages ATF4 signaling for cancer cell survival
Pathria, G., Scott, D. A., Feng, Y., Lee, J. S., Fujita, Y., Zhang, G., Sahu, A. D., Ruppin, E., Herlyn, M., Osterman, A. L., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201899735 · Cited by 163
NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer
Weiss‐Sadan, T., Ge, M., Hayashi, M., Gohar, M., Yao, C.-H., de Groot, A., Harry, S. A., Carlin, A. D., Fischer, H., Shi, L., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.012 · Cited by 159
Nwosu, Z. C., Battello, N., Rothley, M., Piorońska, W., Sitek, B., Ebert, M. P. A., Hofmann, U., Sleeman, J. P., Wölfl, S., Meyer, C., et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0872-6 · Cited by 156
Pyruvate and metabolic flexibility: illuminating a path toward selective cancer therapies
Olson, K. A., Schell, J. C., & Rutter, J. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.01.002 · Cited by 154
Tumour metabolism and its unique properties in prostate adenocarcinoma
Bader, D. A., & McGuire, S. E. (2020) · Nature Reviews Urology · doi:10.1038/s41585-020-0288-x · Cited by 162
Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD+ to alleviate mitochondrial disease
Liu, S., Fu, S., Wang, G., Cao, Y., Li, L., Li, X., Yang, J. J., Li, N., Shan, Y., Cao, Y., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.06.013 · Cited by 159
Metabolism Controls the Balance of Th17/T-Regulatory Cells
Sun, L., Fu, J., & Zhou, Y. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01632 · Cited by 167
Aspartic Acid in Health and Disease
Holeček, M. (2023) · Nutrients · doi:10.3390/nu15184023 · Cited by 151
The Mitochondrial Complex(I)ty of Cancer
Urra, F. A., Muñoz, F., Lovy, A., & Cárdenas, C. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00118 · Cited by 149
Gallipoli, P., Giotopoulos, G., Tzelepis, K., Costa, A. S. H., Vohra, S., Medina-Pérez, P., Basheer, F., Marando, L., Lisio, L. D., Dias, J. M. L., et al. (2018) · Blood · doi:10.1182/blood-2017-12-820035 · Cited by 158
Mullen, P. J., Garcia, G., Purkayastha, A., Matulionis, N., Schmid, E. W., Momcilovic, M., Sen, C., Langerman, J., Ramaiah, A., Shackelford, D. B., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22166-4 · Cited by 149
The redox requirements of proliferating mammalian cells
Hosios, A. M., & Heiden, M. G. V. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000239 · Cited by 157
Self-citationpH-Modulated luminescence switching in a Eu-MOF: rapid detection of acidic amino acids
Zhao, Y., Wan, M., Bai, J., Zeng, H., Lu, W., & Li, D. (2019) · Journal of Materials Chemistry A · doi:10.1039/c9ta00384c · Cited by 146
The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells
Prochownik, E. V., & Wang, H. (2021) · Cells · doi:10.3390/cells10040762 · Cited by 150
Rohlenová, K., Sachaphibulkij, K., Štursa, J., Bezawork‐Geleta, A., Blecha, J., Endaya, B., Werner, L., Černý, J., Zobalová, R., Goodwin, J., et al. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6677 · Cited by 144
Mitochondrial Function and Cell Size: An Allometric Relationship
Miettinen, T. P., & Björklund, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.02.006 · Cited by 151
Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy
Li, Y., Liu, J., Chen, Y., Weichselbaum, R. R., & Lin, W. (2024) · Advanced Science · doi:10.1002/advs.202310309 · Cited by 144
Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation
Wu, B., Zhao, T. V., Jin, K., Hu, Z., Abdel, M. P., Warrington, K. J., Goronzy, J. J., & Weyand, C. M. (2021) · Nature Immunology · doi:10.1038/s41590-021-01065-2 · Cited by 141
EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection
Olenchock, B. A., Moslehi, J. J., Baik, A. H., Davidson, S. M., Williams, J., Gibson, W. J., Chakraborty, A. A., Pierce, K. A., Miller, C. M., Hanse, E. A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.006 · Cited by 145
Self-citationMitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria
Nowinski, S. M., Solmonson, A., Rusin, S. F., Maschek, J. A., Bensard, C., Fogarty, S., Jeong, M.-Y., Lettlová, S., Berg, J. A., Morgan, J. T., et al. (2020) · eLife · doi:10.7554/elife.58041 · Cited by 141
Fernandez, H. R., Gadre, S. M., Tan, M., Graham, G. T., Mosaoa, R., Ongkeko, M. S., Kim, K. A., Riggins, R. B., Parasido, E., Petrini, I., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0101-z · Cited by 144
Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53
Riscal, R., Schrepfer, E., Arena, G., Cissé, M. Y., Bellvert, F., Heuillet, M., Rambow, F., Bonneil, É., Sabourdy, F., Vincent, C., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.033 · Cited by 146
Polyunsaturated Fatty Acid Desaturation Is a Mechanism for Glycolytic NAD+ Recycling
Kim, W., Deik, A., González, C., Gonzalez, M. E., Fu, F., Ferrari, M., Churchhouse, C. L., Florez, J. C., Jacobs, S. B. R., Clish, C. B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.023 · Cited by 144
Altered Signaling Pathways in Prostate Cancer Drive Metabolic Fate
Antico Arciuch, V. G., Gueron, G., Cotignola, J. H., & Vazquez, E. S. (2017) · CONICET Digital (CONICET) · Cited by 139
Defective NADPH production in mitochondrial disease complex I causes inflammation and cell death
Balsa, E., Perry, E. A., Bennett, C. F., Jedrychowski, M. P., Gygi, S. P., Doench, J. G., & Puigserver, P. (2020) · Nature Communications · doi:10.1038/s41467-020-16423-1 · Cited by 141
Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism
Ryan, D. G., Yang, M., Prag, H. A., Blanco, G. R., Nikitopoulou, E., Segarra-Mondejar, M., Powell, C. A., Young, T., Burger, N., Miljković, J. L., et al. (2021) · eLife · doi:10.7554/elife.72593 · Cited by 140
Biochemical Underpinnings of Immune Cell Metabolic Phenotypes
Olenchock, B. A., Rathmell, J. C., & Heiden, M. G. V. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.013 · Cited by 141
Metabolic requirements for cancer cell proliferation
Keibler, M. A., Wasylenko, T. M., Kelleher, J. K., Iliopoulos, O., Heiden, M. G. V., & Stephanopoulos, G. N. (2016) · Cancer & Metabolism · doi:10.1186/s40170-016-0156-6 · Cited by 141
Libiad, M., Vitvitsky, V., Bostelaar, T., Bak, D. W., Lee, H., Sakamoto, N., Fearon, E. R., Lyssiotis, C. A., Weerapana, E., & Banerjee, R. V. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009442 · Cited by 136
Glutamine metabolism in breast cancer and possible therapeutic targets
Li, S., Zeng, H., Fan, J., Wang, X., Xu, C., Li, Y., Tu, J., Nephew, K. P., & Long, X. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115464 · Cited by 143
Extracellular vesicles are independent metabolic units with asparaginase activity
Iraci, N., Gaude, E., Leonardi, T., Costa, A. S. H., Cossetti, C., Peruzzotti-Jametti, L., Bernstock, J. D., Saini, H. K., Gelati, M., Vescovi, A. L., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2422 · Cited by 134
Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR
Kaspar, S., Oertlin, C., Szczepanowska, K., Kukat, A., Senft, K., Lucas, C., Brodesser, S., Hatzoglou, M., Larsson, O. S., Topisirović, I., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf0971 · Cited by 138
Schwartz, A. J., Goyert, J. W., Solanki, S. A., Kerk, S. A., Chen, B., Castillo, C., Hsu, P. P., Do, B. T., Singhal, R., Dame, M. K., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00406-7 · Cited by 133
Lord, S., Cheng, W., Liu, D., Gaude, E., Haider, S. A., Metcalf, T., Patel, N., Teoh, E., Gleeson, F. V., Bradley, K. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.021 · Cited by 133
Metabolic Fitness and Plasticity in Cancer Progression
McGuirk, S., Audet-Delage, Y., & St‐Pierre, J. (2020) · Trends in cancer · doi:10.1016/j.trecan.2019.11.009 · Cited by 133
Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase
Landry, A. P., Ballou, D. P., & Banerjee, R. V. (2020) · ChemBioChem · doi:10.1002/cbic.202000661 · Cited by 134
Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia
Stuani, L., Sabatier, M., Wang, F., Poupin, N., Bosc, C., Saland, E., Castelli, F. A., Gales, L., Montersino, C., Boët, E., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20200924 · Cited by 143
De novo pyrimidine biosynthetic complexes support cancer cell proliferation and ferroptosis defence
Yang, C., Zhao, Y., Wang, L., Guo, Z., Ma, L., Yang, R., Wu, Y., Li, X., Niu, J., Chu, Q., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01146-4 · Cited by 131
The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity
Vatrinet, R., Leone, G., Luise, M. D., Girolimetti, G., Vidone, M., Gasparre, G., & Porcelli, A. M. (2017) · Cancer & Metabolism · doi:10.1186/s40170-017-0165-0 · Cited by 133
Extracellular serine controls epidermal stem cell fate and tumour initiation
Baksh, S. C., Todorova, P. K., Gur-Cohen, S., Hurwitz, B., Ge, Y., Novak, J. S. S., Tierney, M. T., dela Cruz-Racelis, J., Fuchs, E., & Finley, L. W. S. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0525-9 · Cited by 128
Ochocki, J. D., Khare, S., Hess, M., Ackerman, D., Qiu, B., Daisak, J. I., Worth, A. J., Lin, N., Lee, P., Xie, H. J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.04.009 · Cited by 128
Reprogramming of serine, glycine and one-carbon metabolism in cancer
Li, A. M., & Ye, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165841 · Cited by 127
Wong, C. C., Qian, Y., Li, X., Xu, J., Kang, W., TONG, J. H. M., To, K., Ye, J., Li, W., Chen, H., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.011 · Cited by 129
Amplification of USP13 drives ovarian cancer metabolism
Han, C., Yang, L., Choi, H. H., Baddour, J., Achreja, A., Liu, Y., Li, Y., Li, J., Wan, G., Huang, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms13525 · Cited by 127
Chen, W. W., Freinkman, E., & Sabatini, D. M. (2017) · Nature Protocols · doi:10.1038/nprot.2017.104 · Cited by 131
Self-citationAgudelo, L. Z., Ferreira, D. M. S., Dadvar, S., Červenka, I., Ketscher, L., Izadi, M., Zhengye, L., Furrer, R., Handschin, C., Venckūnas, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10712-0 · Cited by 131
Zhang, Z., Liu, R., Shuai, Y., Huang, Y., Jin, R., Wang, X., & Luo, J. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0637-9 · Cited by 125
Redox Regulation in Cancer Cells during Metastasis
Tasdogan, A., Ubellacker, J. M., & Morrison, S. J. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0558 · Cited by 129
Role of amino acid metabolism in mitochondrial homeostasis
Li, Q., & Hoppe, T. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1127618 · Cited by 129
Mitochondrial Complex I Activity Is Required for Maximal Autophagy
Thomas, H. E., Zhang, Y., Stefely, J. A., Veiga, S. R., Thomas, G., Kozma, S. C., & Mercer, C. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.101 · Cited by 123
Functional Assessment of Lipoyltransferase-1 Deficiency in Cells, Mice, and Humans
Ni, M., Solmonson, A., Pan, C., Yang, C., Li, D., Notzon, A., Cai, L., Guevara, G., Zacharias, L. G., Faubert, B., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.005 · Cited by 124
A ROS-dependent mechanism promotes CDK2 phosphorylation to drive progression through S phase
Kirova, D., Judasová, K., Vorhauser, J., Zerjatke, T., Leung, J. K., Glauche, I., & Mansfeld, J. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.06.008 · Cited by 125
Systematic Quantification of Population Cell Death Kinetics in Mammalian Cells
Forcina, G. C., Conlon, M., Wells, A. C., Cao, J. Y., & Dixon, S. J. (2017) · Cell Systems · doi:10.1016/j.cels.2017.05.002 · Cited by 122
Methionine synthase is essential for cancer cell proliferation in physiological folate environments
Sullivan, M. R., Darnell, A. M., Reilly, M. F., Kunchok, T., Joesch-Cohen, L. M., Rosenberg, D. W., Ali, A., Rees, M. G., Roth, J. A., Lewis, C. A., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00486-5 · Cited by 120
Metadata
- Authors
- Sullivan, L. B., Gui, D. Y., Hosios, A. M., Bush, L. N., Freinkman, E., & Vander Heiden, M. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Whitehead Institute for Biomedical Research (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 162
- Issue
- 3
- Pages
- 552-563
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4522278
- OpenAlex
- W1553978925
- Cited by
- 1,173
- References
- 55
- Citations by year
- 2026: 106 · 2025: 95 · 2024: 97 · 2023: 120 · 2022: 151 · 2021: 129 · 2020: 128 · 2019: 90 · 2018: 98 · 2017: 75 · 2016: 71 · 2015: 11
- FWCI
- 28.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (GG006413)
- National Cancer Institute (P30CA1405141, R01CA168653, P30CA014051)
- National Institute of General Medical Sciences (T32GM007753, T32GM007287)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- mitochondrial respiration, aspartate biosynthesis, cell proliferation, electron acceptors, pyruvate, alpha-ketobutyrate, respiratory chain deficiency, auxotrophy, alternative electron acceptors
- MeSH terms
- Adenosine Triphosphate, Aspartic Acid, Butyrates, Electrons, Humans, Mitochondria, Nucleotides, Cell Respiration, Pyruvic Acid, Cell Line, Tumor, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
