NHX-5, an endosomal Na+/H+ exchanger, is associated with metformin action

MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods

Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., & Kumar, S. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msr121 · Cited by 39,795 · see citing works

Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action

Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants

Zhou, B., Lu, Y., Hajifathalian, K., Bentham, J., Di Cesare, M., Danaei, G., Bixby, H., Cowan, M., Ali, M., Taddei, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00618-8 · Cited by 4,311 · see citing works

National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants

Danaei, G., Finucane, M. M., Lu, Y., Singh, G. M., Cowan, M. J., Paciorek, C. J., Lin, J. K., Farzadfar, F., Khang, Y.-H., Stevens, G. A., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60679-x · Cited by 3,568 · see citing works

The Nematode Caenorhabditis elegans

Wood, W. B. (1988) · Cold Spring Harbor Laboratory eBooks · Cited by 2,821 · see citing works

Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain

OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157 · see citing works

Metformin

Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726 · see citing works

Metformin: from mechanisms of action to therapies

Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.018 · Cited by 1,501 · see citing works

Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I

El-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399 · see citing works

Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.-M., Braddock, D. T., Albright, R. A., Prigaro, B. J., Wood, J. L., Bhanot, S., MacDonald, M. J., et al. (2014) · Nature · doi:10.1038/nature13270 · Cited by 1,284 · see citing works

Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in <i>C. elegans</i>

Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.-L., Hall, D. H., & Levine, B. (2003) · Science · doi:10.1126/science.1087782 · Cited by 1,270 · see citing works

Potential therapeutic applications of autophagy

Rubinsztein, D. C., Gestwicki, J. E., Murphy, L. O., & Klionsky, D. J. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2272 · Cited by 1,004 · see citing works

Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism

Cabreiro, F., Au, C., Leung, K.-Y., Vergara-Irigaray, N., Cochemé, H. M., Noori, T., Weinkove, D., Schuster, E., Greene, N. D. E., & Gems, D. (2013) · Cell · doi:10.1016/j.cell.2013.02.035 · Cited by 967 · see citing works

Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP

Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013) · Nature · doi:10.1038/nature11808 · Cited by 828 · see citing works

Molecular cloning, primary structure, and expression of the human growth factor-activatable antiporter

Sardet, C., Franchi, A. J., & Pouysségur, J. (1989) · Cell · doi:10.1016/0092-8674(89)90901-x · Cited by 774 · see citing works

Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation

Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773 · see citing works

Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map

Wicks, S. R., Yeh, R. T., Gish, W. R., Waterston, R., & Plasterk, R. H. A. (2001) · Nature Genetics · doi:10.1038/88878 · Cited by 649 · see citing works

Basic culture methods.

Lewis, J. A., & Fleming, J. T. (1995) · PubMed · Cited by 606 · see citing works

The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism

Zhang, C., Jiang, B., Li, M., Zhu, M., Peng, Y., Zhang, Y., Wu, Y., Li, T. Y., Yu, L., Lu, Z., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.06.014 · Cited by 546 · see citing works

The genetics of feeding in Caenorhabditis elegans.

Avery, L. (1993) · Genetics · doi:10.1093/genetics/133.4.897 · Cited by 500 · see citing works

ESCRT-III Dysfunction Causes Autophagosome Accumulation and Neurodegeneration

Lee, J., Beigneux, A. P., Ahmad, S. T., Young, S. G., & Gao, F. (2007) · Current Biology · doi:10.1016/j.cub.2007.07.029 · Cited by 490 · see citing works

Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice

Xie, Z., Lau, K., Eby, B., Lozano, P., He, C., Pennington, B., Li, H., Rathi, S., Dong, Y., Tian, R., et al. (2011) · Diabetes · doi:10.2337/db10-0351 · Cited by 490 · see citing works

Chapter 1 Basic Culture Methods

Lewis, J. A., & Fleming, J. T. (1995) · Methods in cell biology · doi:10.1016/s0091-679x(08)61381-3 · Cited by 481 · see citing works

Molecular mechanism of action of metformin: old or new insights?

Rena, G., Pearson, E. R., & Sakamoto, K. (2013) · Diabetologia · doi:10.1007/s00125-013-2991-0 · Cited by 479 · see citing works

Metformin Inhibits the Inflammatory Response Associated With Cellular Transformation and Cancer Stem Cell Growth

Hirsch, H. A., Iliopoulos, D., & Struhl, K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221055110 · Cited by 440 · see citing works

Membrane fusion activity of the influenza virus hemagglutinin. The low pH-induced conformational change.

Doms, R. W., Helenius, A., & White, J. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89461-3 · Cited by 340 · see citing works

Metformin inhibits melanoma development through autophagy and apoptosis mechanisms

Tomić, T., Botton, T., Cerezo, M., Robert, G., Luciano, F., Puissant, A., Gounon, P., Allégra, M., Bertolotto, C., Bereder, J. M., et al. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.86 · Cited by 301 · see citing works

Dual roles of autophagy in the survival of <i>Caenorhabditis elegans</i> during starvation

Kang, C., You, Y.-J., & Avery, L. (2007) · Genes &amp; Development · doi:10.1101/gad.1573107 · Cited by 294 · cited 2× · see citing works

Repositioning metformin for cancer prevention and treatment

Quinn, B. J., Kitagawa, H., Memmott, R. M., Gills, J. J., & Dennis, P. A. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.05.004 · Cited by 284 · see citing works

Genetic Analysis of Lysosomal Trafficking in Caenorhabditis elegans

Hermann, G. J., Schroeder, L. K., Hieb, C. A., Kershner, A. M., Rabbitts, B. M., Fonarev, P., Grant, B. D., & Priess, J. R. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0060 · Cited by 279 · see citing works

Structure of Atg5·Atg16, a Complex Essential for Autophagy

Matsushita, M., Suzuki, N. N., Obara, K., Fujioka, Y., Ohsumi, Y., & Inagaki, F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609876200 · Cited by 249 · see citing works

Molecular Cloning and Characterization of a Novel (Na+,K+)/H+ Exchanger Localized to the trans-Golgi Network

Numata, M., & Orlowski, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101319200 · Cited by 244 · see citing works

SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome

Gilfillan, G. D., Selmer, K. K., Roxrud, I., Smith, R., Kyllerman, M., Eiklid, K., Kroken, M., Mattingsdal, M., Egeland, T., Stenmark, H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.013 · Cited by 232 · see citing works

Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila

Slack, C., Foley, A., & Partridge, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047699 · Cited by 199 · see citing works

A point mutation of the Na+/H+ exchanger gene (NHE1) and amplification of the mutated allele confer amiloride resistance upon chronic acidosis.

Counillon, L., Franchi, A. J., & Pouysségur, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4508 · Cited by 167 · see citing works

Christianson Syndrome Protein NHE6 Modulates TrkB Endosomal Signaling Required for Neuronal Circuit Development

Ouyang, Q., Lizarraga, S. B., Schmidt, M., Yang, U., Gong, J., Ellisor, D., Kauer, J. A., & Morrow, E. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.043 · Cited by 147 · see citing works

The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells

Sahra, I. B., Tanti, J., & Bost, F. (2010) · Autophagy · doi:10.4161/auto.6.5.12434 · Cited by 116 · see citing works

X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal–lysosomal dysfunction

Strømme, P., Dobrenis, K., Sillitoe, R. V., Gulinello, M. E., Ali, N. F., Davidson, C. D., Micsenyi, M. C., Stephney, G. W., Ellevog, L., Klungland, A., et al. (2011) · Brain · doi:10.1093/brain/awr250 · Cited by 98 · see citing works

Organellar Na+/H+ Exchangers: Novel Players in Organelle pH Regulation and Their Emerging Functions

Ohgaki, R., van IJzendoorn, S. C. D., Matsushita, M., Hoekstra, D., & Kanazawa, H. (2010) · Biochemistry · doi:10.1021/bi101082e · Cited by 98 · see citing works

Starvation activates MAP kinase through the muscarinic acetylcholine pathway in Caenorhabditis elegans pharynx

You, Y., Kim, J., Cobb, M. H., & Avery, L. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.012 · Cited by 95 · see citing works

MAQGene: software to facilitate C. elegans mutant genome sequence analysis

Bigelow, H., Doitsidou, M., Sarin, S., & Hobert, O. (2009) · Nature Methods · doi:10.1038/nmeth.f.260 · Cited by 95 · see citing works

A TRPV Channel Modulates C. elegans Neurosecretion, Larval Starvation Survival, and Adult Lifespan

Lee, B. H., & Ashrafi, K. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000213 · Cited by 94 · see citing works

The NHX Family of Na+-H+ Exchangers in Caenorhabditis elegans

Nehrke, K. W., & Melvin, J. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203200200 · Cited by 78 · see citing works

Induction of autophagy in ESCRT mutants is an adaptive response for cell survival in C. elegans

Djeddi, A., Michelet, X., Culetto, E., Alberti, A., Barois, N., & Legouis, R. (2012) · Journal of Cell Science · doi:10.1242/jcs.091702 · Cited by 56 · see citing works

Effects of Essential Oil from Hinoki Cypress, Chamaecyparis obtusa, on Physiology and Behavior of Flies

Lee, S.-H., Do, H.-S., & Min, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0143450 · Cited by 54 · see citing works

Autophagy Dysfunction and its Link to Alzheimer’s Disease and Type II Diabetes Mellitus

Wilson, C. M., Magnaudeix, A., Yardin, C., & Terro, F. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113126660146 · Cited by 51 · see citing works

Metabolic Rate Regulates L1 Longevity in C. elegans

Lee, I., Hendrix, A., Kim, J., Yoshimoto, J., & You, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044720 · Cited by 44 · see citing works

Quantitative Proteomic Analysis of the Adipocyte Plasma Membrane

Prior, M. J., Larance, M., Lawrence, R., Soul, J., Humphrey, S. J., Burchfield, J. G., Kistler, C., Davey, J. R., La-Borde, P. J., Buckley, M. J., et al. (2011) · Journal of Proteome Research · doi:10.1021/pr200446r · Cited by 31 · see citing works

Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells

Park, D.-B. (2015) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2015.39.6.518 · Cited by 31 · see citing works

Metformin: Is it a drug for all reasons and diseases?

Triggle, C. R., Mohammed, I., Bshesh, K., Marei, I., Ye, K., Ding, H., MacDonald, R. S., Hollenberg, M. D., & Hill, M. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155223 · Cited by 282 · see citing works

Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions

Apostolova, N., Iannantuoni, F., Gruevska, A., Muntané, J., Rocha, M., & Víctor, V. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101517 · Cited by 201 · see citing works

AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System

Jia, J., Bissa, B., Brecht, L., Allers, L., Choi, S. W., Gu, Y., Zbinden, M., Burge, M. R., Timmins, G. S., Hallows, K. R., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.028 · Cited by 194 · see citing works

The effects of metformin on autophagy

Lu, G., Wu, Z., Shang, J., Xie, Z., Chen, C., & zhang, C. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111286 · Cited by 179 · see citing works

Metformin and Aging: A Review

Glossmann, H. H., & Lutz, O. M. D. (2019) · Gerontology · doi:10.1159/000502257 · Cited by 149 · see citing works

Skeletal Muscle-Released Extracellular Vesicles: State of the Art

Rome, S., Forterre, A., Mizgier, M. L., & Bouzakri, K. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00929 · Cited by 139 · see citing works

Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin

Chen, L., Wang, J., You, Q., He, S., Meng, Q., Gao, J., Wu, X., Shen, Y., Sun, Y., Wu, X., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00761 · Cited by 108 · see citing works

Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing

Varghese, E., Samuel, S. M., Líšková, A., Kubatka, P., & Büsselberg, D. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009634 · Cited by 64 · see citing works

Regulation of organelle function by metformin

Kim, J., & You, Y. (2017) · IUBMB Life · doi:10.1002/iub.1633 · Cited by 49 · see citing works

A DNA nanodevice for mapping sodium at single-organelle resolution

Zou, J., Mitra, K., Anees, P., Oettinger, D., Ramirez, J. R., Veetil, A. T., Gupta, P., Rao, R., Smith, J. J., Kratsios, P., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01950-1 · Cited by 46 · see citing works

Drosophila Models to Investigate Insulin Action and Mechanisms Underlying Human Diabetes Mellitus

Inoue, Y. H., Katsube, H., & Hinami, Y. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0529-0_13 · Cited by 37 · see citing works

Histone deacetylase–mediated regulation of endolysosomal pH

Prasad, H., & Rao, R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002025 · Cited by 34 · see citing works

The Effectiveness of Antidiabetic Drugs in Treating Dementia: A Peek into Pharmacological and Pharmacokinetic Properties

Ogura, J., & Yamaguchi, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126542 · Cited by 17 · see citing works

Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?

Papini, N., Giussani, P., & Tringali, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168884 · Cited by 15 · see citing works

Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer

Prasad, H., Harshavardhan, B. V., Subbalakshmi, A. R., Mandal, S., Jolly, M. K., & Visweswariah, S. S. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00463-0 · Cited by 6 · see citing works

Insulin may increase disease severity and mortality of COVID-19 through Na+/H+ exchanger in patients with type 1 and type 2 diabetes mellitus

Cüre, E., & Cüre, M. C. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01951-y · Cited by 5 · see citing works

An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression

Prasad, H., Mandal, S., Mathew, J. K. K., Cherukunnath, A., Duddu, A. S., Banerjee, M., Ramani, H., Bhat, R., Jolly, M. K., & Visweswariah, S. S. (2024) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-23-0606 · Cited by 5 · see citing works

Where and How in the mTOR Pathway Inhibitors Fight Aging: Rapamycin, Resveratrol, and Metformin

Arbor, S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79338 · Cited by 5 · see citing works

Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated worms

Tan, J., Chiamkunakorn, C., Boonchuay, K., Shi, Y., Braeckman, B. P., & Suthammarak, W. (2025) · PLoS ONE · doi:10.1371/journal.pone.0326100 · Cited by 2 · see citing works

Using genetics to inform new therapeutics for diabetes

Yu, A. C.-S., Li, J., & Chan, T. (2017) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2017.1323631

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na+/H+ exchanger

Cüre, M. C., & Cüre, E. (2023) · World Journal of Virology · doi:10.5501/wjv.v12.i1.12

Metformin sensitizes hepatocellular carcinoma to sorafenib by facilitating NHE1 degradationPreprint

Tian, G., Yu, J., Yan, L., Ye, F., Gui, Y., Li, J. V., Yang, S., Zou, L., Zhang, L., & Zhao, L. (2023) · Research Square · doi:10.21203/rs.3.rs-3061872/v1

The Endosomal pH Regulator NHE6 is Required for Insulin-Stimulated Glucose Uptake in AdipocytesPreprint

Mekile, A. X., Makena, M. R., Gupta, R., White, C. J., Bowman, R. W., Patnayak, R. L., Lorenzo, D. N., & Rao, R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.30.551163

The Christianson syndrome protein, sodium hydrogen exchanger isoform 6, is required for fat accumulation

Gupta, R., Mekile, A. X., Patnayak, R. L., Makena, M. R., Bowman, R. W., White, C. J., Lorenzo, D. N., & Rao, R. (2025) · The Journal of Physiology · doi:10.1113/jp289613

Metformin's hidden power: Unveiling its role in melanoma suppression through endo-lysosome pH and autophagy regulation

Chang, X., Wang, X., Wang, M., Tan, Y., Xie, Y., Li, D., Ma, H., Cai, F., Zhuang, H., & Hua, Z. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178438

Metformin Inhibits Na+/H+ Exchanger NHE3 Resulting in Intestinal Water Loss

Han, Y., & Yun, C. C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.867244 · Cited by 16 · see citing works

Clathrin-mediated Endocytosis and Recycling of the Neuron-specific Na+/H+ Exchanger NHE5 Isoform

Szászi, K., Paulsen, A., Szabó, E. Z., Numata, M., Grinstein, S., & Orlowski, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206629200 · Cited by 62 · see citing works

Endosomal Na+/H+exchanger NHE5 influences MET recycling and cell migration

Fan, S. H. Y., Numata, Y., & Numata, M. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-04-0257 · Cited by 21 · see citing works

The yeast endosomal NaM/HM exchanger, Nhx1,

Nass, R., & Rao, R. (2015)

Na+/H+ exchanger isoform 6 (NHE6/SLC9A6) is involved in clathrin-dependent endocytosis of transferrin

Xinhan, L., Matsushita, M., Numaza, M., Taguchi, A., Mitsui, K., & Kanazawa, H. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00154.2011 · Cited by 67 · see citing works