The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2
Open accessAbstract
Repression of mitochondrial respiration represents an evolutionarily ancient cellular adaptation to hypoxia and profoundly influences cell survival and function; however, the underlying molecular mechanisms are incompletely understood. Primarily utilizing pulmonary arterial endothelial cells as a representative hypoxic cell type, we identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210 (miR-210). ISCU1/2 facilitate the assembly of iron-sulfur clusters, prosthetic groups that are critical for electron transport and mitochondrial oxidation-reduction reactions. Under in vivo conditions of upregulating miR-210 and repressing ISCU1/2, the integrity of iron-sulfur clusters is disrupted. In turn, by repressing ISCU1/2 during hypoxia, miR-210 decreases the activity of prototypical iron-sulfur proteins controlling mitochondrial metabolism, including Complex I and aconitase. Consequently, miR-210 represses mitochondrial respiration and associated downstream functions. These results identify important mechanistic connections among microRNA, iron-sulfur cluster biology, hypoxia, and mitochondrial function, with broad implications for cellular metabolism and adaptation to cellular stress.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The coordinate metabolic changes caused by HIF-1 that alter mitochondrial function are attributable, in part, to the HIF-1-mediated transcriptional upregulation of microRNA 210 (miR210), which specifically inhibits Fe-S complex formation to alter mitochondrial bioenergetics and ROS production (Pasteur effect) (69).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
Experimental — accuracy not yet measuredIn the citing paper
“Interestingly, during normoxia, forced expression of miR210 caused an increase in ROS generation (69, 81), possibly due to deficiencies in complex I that may promote electron leak in the presence of molecular oxygen.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
In the citing paper
“Nonetheless, experimental evidence suggests that enhanced ROS production is not a sustained event in hypoxia (69, 385).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
In the citing paper
“Within mitochondria it targets regulatory proteins that assist in the assembly of the complexes of the electron transport chain, and suppresses respiration (103, 108).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [103]
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
1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601 · cited 1×
“Mitophagy has been characterized as a HIF-dependent mechanism (Zhang et al., 2008).”
BackgroundRetractedKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · cited 1×
“First, by induction of PDK1, HIF-1a decreases the activity of the TCA cycle, increases glycolysis, and reduces mitochondrial electron flux (Kim et al., 2006).”
Iron-sulfur clusters: nature's modular, multipurpose structures
Beinert, H., Holm, R. H., & Münck, E. (1997) · Science · doi:10.1126/science.277.5326.653 · Cited by 1,944 · cited 4×
“280 Cell Metabolism 10, 273–284, October 7, 2009 ª2009 Elsevier Inc. to oxidative stress (Beinert et al., 1997), along with repression of iron-sulfur cluster biogenesis via downregulated ISCU1/2, may provide a real-time redox-sensitive ‘‘switch’’ that is triggered by hypoxia to induce downstream…”
InfluentialHIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells
Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225 · cited 1×
“Second, HIF-1a induces a COX4-1 to COX4-2 subunit switch during hypoxia to improve the efficiency of electron transfer to oxygen at Complex IV (Fukuda et al., 2007).”
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154 · cited 1×
“Conditions were based on studies of hypoxic exposure of HPAECs (Manalo et al., 2005) to allow for steady-state adaptation without nonspecific cell death.”
A MicroRNA Signature of Hypoxia
Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055 · cited 5×
“…with other studies demonstrating the repression of apoptosis by miR-210 during hypoxia in other cellular contexts (Fasanaro et al., 2008; Kulshreshtha et al., 2007), these data lend credence to a model in which miR-210 carries a maladaptive role during normoxia, causing a mismatch of…”
InfluentialHypoxia-Induced Pulmonary Vascular Remodeling
Stenmark, K. R., Fagan, K. A., & Frid, M. G. (2006) · Circulation Research · doi:10.1161/01.res.0000243584.45145.3f · Cited by 1,001 · cited 2×
“In particular, this response may be especially important to the pulmonary vascular endothelium, which directly responds to hypoxia by controlling the release of vasoactive effectors, thereby critically influencing normal vascular physiology and the development of pulmonary hypertension (Stenmark et al., 2006).”
Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M. C., & Martelli, F. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800731200 · Cited by 912 · cited 6×
“Some, but not all, of these miRNA have been identified in other transformed (Kulshreshtha et al., 2007) or primary endothelial cells (Fasanaro et al., 2008) exposed to hypoxia.”
Influentialhsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer
Camps, C., Buffa, F. M., Colella, S., Moore, J., Sotiriou, C. P., Sheldon, H., Harris, A. L., Gleadle, J., & Ragoussis, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1755 · Cited by 672 · cited 3×
“Additionally, miR-210 is specifically induced by HIF-1a but not HIF-2a (Camps et al., 2008), a second transcriptional regulator of the hypoxic response, which carries partial but not full redundancy in function with HIF-1a (Wang et al., 2005).”
Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells
Seagroves, T. N., Ryan, H. E., Lu, H., Wouters, B. G., Knapp, M., Thibault, P., Laderoute, K. R., & Johnson, R. S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3436-3444.2001 · Cited by 634 · cited 4×
“The elucidation of the miR-210-ISCU1/2 regulatory pathway substantially clarifies the nature of the complex crosstalk between HIF-1a and mitochondria (Seagroves et al., 2001) and complements other HIF-dependent processes proposed to regulate the mismatch of reduced oxygen tension and mitochondrial electron transport.”
Influential
Cited by
Sorted by citations
Items 201–300 of 702
Turning the Oxygen Dial: Balancing the Highs and Lows
Baik, A. H., & Jain, I. H. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.04.005 · Cited by 70
“These include chromatin remodeling, epigenetic changes (TETs and DNA methylation) [51], miRNA expression (also known as ‘hypoxamirs’) [52,53], post-translational processes (e.”
BackgroundMicroRNAs in Skin and Wound Healing
Banerjee, J., & Sen, C. K. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-083-0_26 · Cited by 79
Crosstalk of MicroRNAs and Oxidative Stress in the Pathogenesis of Cancer
Lu, C., Zhou, D., Wang, Q., Liu, W., Yu, F., Wu, F., & Chen, C. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2415324 · Cited by 73
“For instance, it has been revealed that upregulated miR-210 could increase the ROS level in cancer cells by suppressing the iron-sulfur cluster recruiting proteins ISCU1/2 [30, 31].”
BackgroundOkamoto, M., Nasu, K., Abe, W., Aoyagi, Y., Kawano, Y., Kai, K., Moriyama, M., & Narahara, H. (2014) · Human Reproduction · doi:10.1093/humrep/deu332 · Cited by 75
microRNA and Pulmonary Hypertension
Boucherat, O., Potus, F., & Bonnet, S. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-22671-2_12 · Cited by 72
Invited review: decoding the microRNA response to hypoxia
Pocock, R. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0910-5 · Cited by 72
“In addition, miR210 is required for cell survival under a hypoxic microenvironment [14].”
InfluentialMiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes
He, J., Wu, J., Xu, N., Xie, W., Li, M., Li, J., Jiang, Y., Yang, B. B., & Zhang, Y. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks995 · Cited by 70
“MiR-210 also down-regulates mitochondrial function by repressing the expression of iron–sulfur cluster scaffold homolog and COX10 (cytochrome c oxidase assembly protein) (23).”
Self-citationHypoxia and cancer cell metabolism
Huang, D., Li, C., & Zhang, H. (2014) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmt148 · Cited by 73
“Moreover, HIF-1 induces miR-210 transcription, which decreases the expression of iron-sulfur cluster assembly proteins (ISCU) and cytochrome C oxidase assembly protein (COX10), two important elements of the mitochondria electron transport chain and the TCA cycle [20,21].”
BackgroundSuppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate
Yao, Q., Khan, M. P., Merceron, C., LaGory, E. L., Tata, Z., Mangiavini, L., Hu, J., Vemulapalli, K., Chandel, N. S., Giaccia, A. J., et al. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.04.029 · Cited by 71
Maron, B. A., Oldham, W. M., Chan, S. Y., Vargas, S. O., Arons, E., Zhang, Y., Loscalzo, J., & Leopold, J. A. (2014) · Circulation · doi:10.1161/circulationaha.113.007690 · Cited by 73
“We next determined whether changes in cellular mitochondrial content resulted from hypoxia or hypoxia-induced aldosterone synthesis to influence StAR expression/activity in HPAECs.”
BackgroundMethodInfluentialSelf-citationHypoxia and Metabolism in Metastasis
Zhang, T., Suo, C., Zheng, C., & Zhang, H. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12734-3_6 · Cited by 86
MicroRNAs: Small molecules with a large impact on pre‐eclampsia
Hemmatzadeh, M., Shomali, N., Yousefzadeh, Y., Mohammadi, H., Ghasemzadeh, A., & Yousefi, M. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29286 · Cited by 67
“During hypoxia, miR‐210 is characteristically increased by HIF‐1α and controls different pathways associated with hypoxia including angiogenesis, cell survival, mitochondrial metabolism, and DNA repair (Chan et al., 2009; Kulshreshtha et al., 2007).”
BackgroundRegulating microRNA expression: at the heart of diabetes mellitus and the mitochondrion
Hathaway, Q. A., Pinti, M. V., Durr, A. J., Waris, S. A., Shepherd, D. L., & Hollander, J. M. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00520.2017 · Cited by 69
“miRNA-210 is a known negative regulator of iron-sulfur cluster assembly scaffold protein ISCU1/2, which play essential roles in the function of aconitase and complex I of the electron transport chain (23).”
BackgroundHIF-1α Metabolic Pathways in Human Cancer
Elzakra, N., & Kim, Y. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51652-9_17 · Cited by 72
Regulation of Aerobic Glycolysis by microRNAs in Cancer.
Singh, P. K., Mehla, K., Hollingsworth, M. A., & Johnson, K. R. (2011) · PubMed · Cited by 68
Schwarzer, M., Osterholt, M., Lunkenbein, A., Schrepper, A., Amorim, P., & Doenst, T. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.274704 · Cited by 68
“Hypoxia has also been shown to reduce complex I activity by downregulating the expression of ISCU1/2 (Chan et al. 2009), which is required for the assembly of iron–sulfur clusters that are integral parts of the mitochondrial complexes I, II and III (Rouault & Tong, 2008).”
BackgroundTrophoblasts, invasion, and microRNA
Doridot, L., Miralles, F., Barbaux, S., & Vaiman, D. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00248 · Cited by 70
Mitochondrial miRNAs (MitomiRs): Their potential roles in breast and other cancers
Ertürk, E., Onur, O. E., Akgün, O., Tuna, G., Yıldız, Y., & Arı, F. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.08.002 · Cited by 67
MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases
Aranda, J. F., Madrigal‐Matute, J., Rotllán, N., & Fernandez-Hernando, C. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.014 · Cited by 67
“MiR-210 has recently been described to regulate the activity of prototypical iron–sulfur scaffold protein (ISCU), controlling mitochondrial metabolism and free radical response in response to hypoxia [87,88].”
Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism
Pollard, P. J., Yang, M. H., Su, H., Soga, T., & Kranc, K. R. (2014) · Hypoxia · doi:10.2147/hp.s47968 · Cited by 67
“33 Further, HIF1 regulates the expression of micro-RNA mir-210, causing downregulation of the Complex I subunit NDUFA4 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex), Complex II subunit SDHD (subunit D of succinate dehydrogenase [SDH] complex), the iron-sulfur cluster scaffold proteins 1/2 and the cytochrome c o…”
BackgroundBanerjee, J., & Sen, C. K. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-22671-2_15 · Cited by 64
Severino, P., D’Amato, A., Netti, L., Pucci, M., Infusino, F., Maestrini, V., Mancone, M., & Fedele, F. (2019) · Journal of Diabetes Research · doi:10.1155/2019/9489826 · Cited by 63
Influence of microRNA on the Maintenance of Human Iron Metabolism
Davis, M. R., & Clarke, S. L. (2013) · Nutrients · doi:10.3390/nu5072611 · Cited by 63
“…[43] miR-122 HFE, HJV Castoldi et al. (2009) [44] miR-196 BACH1 Hou et al. (2010) [45] miR-200b FTH Shpyleva et al. (2009) [46] miR-210 ISCU, TFR Chan et al. (2009) [47], Yoshioka et al. (2012) [48] miR-214 Lactoferrin Liao et al. (2010) [49] miR-320 TFR Schaar et al. (2009) [50] miR-485-3p…”
BackgroundInfluentialMicroRNAs and the metabolic hallmarks of aging
Victoria, B., López, Y. O. N., & Masternak, M. M. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.12.021 · Cited by 64
“…factor 1α (HIF-1α) and downregulates the expression of iron-sulfur cluster assembly proteins (ISCU1/2) and other subunits of the electron transport chain complexes I and II, therefore directly controlling mitochondrial metabolism and respiration (Chan et al., 2009; Kulshreshtha et al., 2007).”
BackgroundVirga, F., Cappellesso, F., Stijlemans, B., Henze, A., Trotta, R., Audenaerde, J. R. M. V., Mirchandani, A. S., Sánchez-García, M. A., Vandewalle, J., Orso, F., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf0466 · Cited by 67
Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia
Catrina, S. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1166-x · Cited by 65
“ROS production by complex I is also inhibited by HIF-1α via mir210 [37].”
The Use of microRNAs to Modulate Redox and Immune Response to Stroke
Ouyang, Y., Stary, C. M., White, R., & Giffard, R. G. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5757 · Cited by 60
“miR-181a-1* BCL2 (82) miR-181b Importin-a3 (164) miR-181c Mt-COX1 (207) miR-181d BCL2 (183) miR-195 BCL2 (158) miR-210 ISCU1/2, SDHD (29, 30, 116, 144) miR-320 HSP20 (146, 186) miR-338 COXIV, ATP5G1 (9, 10) miR-365-2 BCL2 (158) miR-378* HSP72 (170) miR-451 BCL2 (119) miR-484 Fis1 (179) miR-491-5p BCL-xL (53) miR-497 B…”
Yang, Y., Zhang, J., Xia, T., Li, G., Tao, T., Wang, M., Wang, R., Zhao, L., Yang, Y., Lan, K., et al. (2016) · Oncology Reports · doi:10.3892/or.2016.5129 · Cited by 62
MicroRNAs in brain development and cerebrovascular pathophysiology
Ma, Q., Zhang, L., & Pearce, W. J. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00022.2019 · Cited by 64
“MiR-210 regulates multiple diverse cellular events, including angiogenesis, mitochondrial metabolism, and apoptotic cell death (24, 25, 32, 138).”
BackgroundMyatt, L., Muralimanoharan, S., & Maloyan, A. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-1031-1_12 · Cited by 64
“MiR210 targets ISCU in trophoblast cell lines [ 93 ] possibly by targeting the transcript coding for ISCU, which facilitate the assembly of iron–sulfur clusters that are incorporated into enzymes involved in energy production, including mitochondrial respiratory complexes [ 106 ].”
BackgroundNew strategies for targeting glucose metabolism–mediated acidosis for colorectal cancer therapy
Wang, G., Wang, J., Yin, P., Xu, K., Wang, Y., Shi, F., Gao, J., & Fu, X. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26917 · Cited by 61
“The hypoxia‐responsive miRNAs (HRMs), such as miR‐210, may represent interesting CRC biomarkers as well as target molecules for gene and drug therapy (S. Y. Chan et al., 2009).”
BackgroundDiscerning functional hierarchies of microRNAs in pulmonary hypertension
Negi, V., & Chan, S. Y. (2017) · JCI Insight · doi:10.1172/jci.insight.91327 · Cited by 58
“miR-210 was found to have substantial pleiotropic function in mitochondrial metabolism (45), proliferation (53, 54), and cell survival, thus”
BackgroundResultSelf-citationGokhale, A., Hartwig, C. L., Freeman, A. A. H., Bassell‐Hawkins, J., Zlatic, S. A., Savas, C. S., Vadlamudi, T., Abudulai, F., Pham, T. T., Crocker, A. J., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1983-18.2019 · Cited by 61
“2 chromosomal segment could modulate the mitochondrial proteome acting both in nuclear and mitochondrial encoded RNAs (Bandiera et al., 2011; Chan et al., 2009; Minones-Moyano et al., 2011; Stark et al., 2008; Zhang et al., 2014).”
BackgroundUllmann, P., Qureshi-Baig, K., Rodriguez, F., Ginolhac, A., Nonnenmacher, Y., Ternes, D., Weiler, J., Gäbler, K., Bahlawane, C., Hiller, K., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11772 · Cited by 60
Lin, J., Chuang, C., & Zuo, L. (2017) · Oncotarget · doi:10.18632/oncotarget.14461 · Cited by 60
“The augmented ROS can be attributed to compromised mitochondrial activity as miR-210 inhibits mitochondrial iron-sulfur cluster scaffold homologue and the assembly iron-sulfur cluster [37, 39].”
BackgroundLi, H., Liu, Y., Shang, L., Cai, J., Wu, J., Zhang, W., Pu, X., Dong, W., Qiao, T., & Li, K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820051116 · Cited by 62
“IscU has been revealed to be a member of the miR-210 regulon during hypoxia and adversely controls mitochondrial metabolism (28).”
BackgroundHypoxia Conditioning for High-Altitude Pre-acclimatization
Burtscher, M., Millet, G. P., & Burtscher, J. (2022) · Journal of Science in Sport and Exercise · doi:10.1007/s42978-021-00150-0 · Cited by 68
“1 3 system components [31, 32, 93] are examples of reducing oxygen consumption.”
BackgroundZhao, D.-S., Chen, Y., Jiang, H., Lu, J., Zhang, G., Geng, J., Zhang, Q. H., Shen, J.-H., Xin Min, Z. H. O. U., Zhu, W., et al. (2013) · Cardiovascular Pathology · doi:10.1016/j.carpath.2013.04.001 · Cited by 59
Jung, K.-A., Lee, S., & Kwak, M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6797 · Cited by 60
“Hypoxia-inducible miR-210 targets the iron-sulfur assembly protein ISCU1/2, thereby inhibiting complex I activity (7).”
Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS
Lee, Y., & Im, E. (2021) · Antioxidants · doi:10.3390/antiox10030377 · Cited by 59
Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions
Bargiela, D., Burr, S. P., & Chinnery, P. F. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2018.02.002 · Cited by 60
Hypoxia signaling: Challenges and opportunities for cancer therapy
Ivan, M., Fishel, M. L., Tudoran, O. M., Pollok, K. E., Wu, X., & Smith, P. J. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.10.002 · Cited by 57
Disturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice
He, M., Xu, S., Zhang, X., Wang, Y., Xiong, J., Zhang, X., Lu, Y., Zhang, L., Yu, Z., & Zhou, Z. (2013) · NeuroToxicology · doi:10.1016/j.neuro.2013.05.011 · Cited by 57
Li, Y., Yao, M.-C., Zhou, Q., Cheng, Y., Che, L., Xu, J., Xiao, J., Shen, Z., & Bei, Y. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00282 · Cited by 62
“, 2014), promoting the shift from mitochondria respiration to glycolysis (Chan et al., 2009) and inducing angiogenesis (Fasanaro et al.”
BackgroundLee, J., Heo, J., & Kang, H. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0243-z · Cited by 57
Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function
Moosavi, B., Zhu, X., Yang, W., & Yang, G. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0264 · Cited by 60
Sarg, N. H., Zaher, D. M., Jayab, N. N. A., Mostafa, S. H., Ismail, H. H., & Omar, H. A. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116307 · Cited by 59
Holding Our Breath: The Emerging and Anticipated Roles of microRNA in Pulmonary Hypertension
White, K., Loscalzo, J., & Chan, S. Y. (2012) · Pulmonary Circulation · doi:10.4103/2045-8932.101395 · Cited by 55
“[24] Importantly, a number of these phenotypes in cell culture are directly linked to the ability of miR-210 to downregulate one of its primary target genes, the iron sulfur complex assembly 1/2 (ISCU1/2), in order to repress mitochondrial metabolism in favor of glycolysis (the so-called Pasteur effect).[32] Such a me…”
BackgroundSelf-citationDehydration mediated microRNA response in the African clawed frog Xenopus laevis
Wu, C., Biggar, K. K., & Storey, K. B. (2013) · Gene · doi:10.1016/j.gene.2013.07.064 · Cited by 56
Emerging Metabolic Therapies in Pulmonary Arterial Hypertension
Harvey, L. D., & Chan, S. Y. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6040043 · Cited by 59
“Specifically, miR-210 was found to downregulate expression of the iron-sulfur cluster assembly proteins 1 and 2 (ISCU1/2) [38].”
BackgroundSelf-citationMicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy
Ait‐Aissa, K., Nguyen, Q. M., Gabani, M. H., Kassan, A., Kumar, S., Choi, S. K., González, A. A., Khataei, T., Sahyoun, A. M., Chen, C., et al. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01107-3 · Cited by 57
“miR‐210 Unknown – EC apoptosis and atherosclerosis [125] ISCU 1,2 [124]”
BackgroundFrataxin participates to the hypoxia-induced response in tumors
Guccini, I., Serio, D., Condò, I., Rufini, A., Tomassini, B., Mangiola, A., Maira, G., Anile, C., Fina, D., Pallone, F., et al. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.5 · Cited by 57
“downregulation of the scaffold protein ISCU in order to repress the mitochondrial electron transport and the Krebs’ cycle.(36) However, the repression of ISCU by miR-210”
BackgroundThe biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling
Long, Y. C., Tan, T. M. C., Inoue, T., & Tang, B. L. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00665.2013 · Cited by 57
“For example, miR-210 regulates mitochondrial metabolism during hypoxia by repressing FE-S cluster assembly proteins (23).”
BackgroundMicroRNAs Regulating Reactive Oxygen Species in Cardiovascular Diseases
Gong, Y.-Y., Luo, J., Wang, L., & Huang, Y. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7328 · Cited by 55
“A plausible explanation is that the contribution of different pathways to mitochondrial ROS production varies under different conditions (15).”
The secret messages between mitochondria and nucleus in muscle cell biology
Soledad, R. B., Charles, S., & Das, S. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.03.019 · Cited by 54
Dasgupta, A., Wu, D., Tian, L., Xiong, P. Y., Dunham‐Snary, K. J., Chen, K., Alizadeh, E., Motamed, M., Potus, F., Hindmarch, C. C. T., et al. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190027 · Cited by 64
He, M., Lu, Y., Xu, S., Mao, L., Zhang, L., Duan, W., Liu, C., Pi, H., Zhang, Y., Zhong, M., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.60 · Cited by 54
“These results verified that miR-210 regulates the expression of ISCU1/2 by binding to the predicted target site in the 30-UTR of ISCU1/2.”
BackgroundInfluentialSelf-citationMicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen
Tagscherer, K. E., Fassl, A., Sinkovic, T., Richter, J., Schecher, S., Macher‐Goeppinger, S., & Roth, W. (2016) · Cancer Cell International · doi:10.1186/s12935-016-0321-6 · Cited by 55
“Furthermore, it has been shown that an elevated expression of miR-210 reduces oxygen consumption and upregulates glycolysis in various tumor entities [39, 40, 42, 58].”
BackgroundImpact of MicroRNAs in the Cellular Response to Hypoxia
Bertero, T., Rezzonico, R., Pottier, N., & Mari, B. P. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.03.006 · Cited by 56
Hypoxic Signalling in Tumour Stroma
Laitala, A., & Erler, J. T. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00189 · Cited by 55
An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells
Hale, A., Lee, C., Annis, S., Min, P., Pande, R. L., Creager, M. A., Julian, C. G., MOORE, L. G., Mitsialis, S. A., Hwang, S. J., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.06.012 · Cited by 54
“As previously described [7], Complex I activity was measured by immunocapture and spectrophotometry (A340 nm) reflecting oxidation of NADH to NAD, per the manufacturer's instructions (Mitosciences).”
InfluentialSelf-citationHansmann, G., Plouffe, B. D., Hatch, A., von Gise, A., Sallmon, H., Zamanian, R. T., & Murthy, S. K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0779-6 · Cited by 52
“premenopausal PAH patients and the previously described inverse relation between EPC number and hemodynamic status of PAH patients [16], it will be important to explore the impact of metabolic regulators such as PPARs [41], mitochochondrial regulatory proteins [32], micro RNAs [44, 45], and sex hormones [33, 46] on pu…”
Hypoxia-Induced miR-210 Modulates Tissue Response to Acute Peripheral Ischemia
Zaccagnini, G., Maimone, B., Stefano, V. D., Fasanaro, P., Greco, S., Perfetti, A., Capogrossi, M. C., Gaetano, C., & Martelli, F. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5206 · Cited by 53
“…and cancer cells show that miR-210 is a crucial regulator of mitochondrial metabolism: by downregulating the expression of ISCU1/2, NDU-FA2, COX10, and SDH, miR-210 disrupts the mitochondrial electron transport activity, repressing mitochondrial oxidative phosphorylation (6, 8, 15, 17, 46).”
InfluentialAnton, L., Devine, A., Polyák, E., Olarerin-George, A. O., Brown, A. G., Falk, M. J., & Elovitz, M. A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00699 · Cited by 54
“Additional studies have shown a mechanistic link between miR-210, mitochondrial associated genes and mitochondrial respiration (Chan et al., 2009; Chen et al., 2010; Puisségur et al., 2010).”
BackgroundTune instead of destroy: How proteolysis keeps OXPHOS in shape
Szczepanowska, K., & Trifunović, A. (2021) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2020.148365 · Cited by 51
Kucejová, B., Sunny, N. E., Nguyen, A. D., Hallac, R. R., Fu, X., Peña‐Llopis, S., Mason, R. P., DeBerardinis, R. J., Xie, X.-J., DeBose‐Boyd, R. A., et al. (2011) · Oncogene · doi:10.1038/onc.2010.587 · Cited by 51
“One mechanism may involve the Fe-S cluster assembly proteins IscU1/2, which are regulated by pVhl in a miR-210-dependent manner (Chan et al., 2009), and which we found to be downregulated in Ad-Cre Vhl livers.”
InfluentialTherapeutic opportunities for senolysis in cardiovascular disease
Sweeney, M. D., Cook, S. A., & Gil, J. (2022) · FEBS Journal · doi:10.1111/febs.16351 · Cited by 54
Yan, X., Zhou, M., Wang, J., Zhao, Y., Li, S., Zhou, B., Su, Z., Xu, C., Xia, Y., Qian, H., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.01.007 · Cited by 51
“lism and angiogenesis by targeting E2F3, MYC antagonist (MNT), ephrinA3 (EFNA3) and iron-sulfur cluster scaffold protein (ISCU) [6,7,40–45].”
The Effect of Intra-articular Injection of MicroRNA-210 on Ligament Healing in a Rat Model
Shoji, T., Nakasa, T., Yamasaki, K., Kodama, A., Miyaki, S., Niimoto, T., Okuhara, A., Kamei, N., Adachi, N., & Ochi, M. (2012) · The American Journal of Sports Medicine · doi:10.1177/0363546512458894 · Cited by 51
Overexpression of miR-210 and its significance in ischemic tissue damage
Zaccagnini, G., Maimone, B., Fuschi, P., Maselli, D., Spinetti, G., Gaetano, C., & Martelli, F. (2017) · Scientific Reports · doi:10.1038/s41598-017-09763-4 · Cited by 51
Yu, Q., & Chan, S. Y. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63245-2_24 · Cited by 51
“Correspondingly, in PAECs from PH mice, downregulation of a separate Fe-S biogenesis gene, ISCU, in PAECs was observed, compromising integrity of Fe-S clusters [64], repressing mitochondrial oxidative phosphorylation, increasing ROS, and promoting PH in mice.”
BackgroundSelf-citationXu, K., Lu, C., Ren, X., Wang, J., Xu, P., & Zhang, Y. (2021) · Environmental Toxicology · doi:10.1002/tox.23327 · Cited by 51
Self-citationA Complex Genome-MicroRNA Interplay in Human Mitochondria
Shinde, S., & Bhadra, U. (2015) · BioMed Research International · doi:10.1155/2015/206382 · Cited by 49
“These cell organelles play a vital cellular function, which is required in the fine-tuning of the posttranscriptional regulation by an alternative pathway [13].”
BackgroundTang, Y., Hou, Y., Zeng, Y., Hu, Y., Zhang, Y., Wang, X., & Meng, X. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174617 · Cited by 50
Self-citationHypoxamiR-210 accelerates wound healing in diabetic mice by improving cellular metabolism
Narayanan, S., Angelstig, S. E., Xu, C., Grünler, J., Zhao, A. Z., Zhu, W., Xu, N., Ståhle, M., Zhang, J., Ivan, M., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-01495-y · Cited by 47
Valadkhan, S., & Valencia-Hipólito, A. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_489 · Cited by 49
Systems Biology Approaches to Redox Metabolism in Stress and Disease States
Wang, R., Oldham, W. M., Maron, B. A., & Loscalzo, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7256 · Cited by 48
Self-citationHypoxia-Inducible Factor Prolyl 4-Hydroxylases and Metabolism
Koivunen, P., & Kietzmann, T. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.10.004 · Cited by 47
Huang, M., Yang, L., Peng, X., Wei, S., Fan, Q., Yang, S., Li, X., Li, B., Jin, H., Wu, B., et al. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01698-5 · Cited by 54
“Importantly, miR-210 can significantly inhibit ISCU1/2 protein expression, resulting in the destruction of iron-sulfur cluster integrity and limiting ROS production [94, 95].”
BackgroundObstructive Sleep Apnea–induced Endothelial Dysfunction Is Mediated by miR-210
Shang, F., Wang, S., Gongol, B., Han, S. Y., Cho, Y., Schiavon, C. R., Chen, L., Xing, Y., Zhao, Y., Ning, M., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202202-0394oc · Cited by 46
Adipose tissue dysfunction and its effects on tumor metabolism
Diedrich, J. D., Chkourko, H., & Podgorski, I. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0045 · Cited by 47
Sun, W., Zhao, L., Song, X., Zhang, J., Xing, Y., Liu, N., Yan, Y., Li, Z., Lu, Y., Wu, J., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000480417 · Cited by 47
MiR‐210 Links Hypoxia With Cell Proliferation Regulation in Human Laryngocarcinoma Cancer
Zuo, J., Wen, M., Lei, M., Peng, X., Yang, X., & Liu, Z. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25059 · Cited by 45
“Together, miR-210 is involved in a wide variety of normal and pathological cellular processes including cell development, cell death, angiogenesis, metabolism, and oncogenesis [Chan et al., 2009; Huang et al., 2009; Gee et al., 2010; Shen et al., 2013].”
BackgroundResultSen, C. K. (2011) · Physiological Genomics · doi:10.1152/physiolgenomics.00037.2011 · Cited by 45
Gómez-Verján, J. C., Vázquez-Martínez, E. R., Rivero-Segura, N. A., & Medina-Campos, R. H. (2018) · Human Genetics · doi:10.1007/s00439-018-1955-3 · Cited by 46
Iron Deficiency in Pulmonary Arterial Hypertension: A Deep Dive into the Mechanisms
Quatredeniers, M., Mendes‐Ferreira, P., Santos‐Ribeiro, D., Nakhleh, M. K., Ghigna, M., Cohen‐Kaminsky, S., & Perros, F. (2021) · Cells · doi:10.3390/cells10020477 · Cited by 45
“In accordance with these metabolic changes, previous reports attest that hypoxia-induced miR210 expression leads to ISC deficiency and decreased mitochondrial respiration in murine and human pulmonary vascular cells [88].”
BackgroundmiR-210 hypoxamiR in Angiogenesis and Diabetes
Zaccagnini, G., Greco, S., Voellenkle, C., Gaetano, C., & Martelli, F. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0200 · Cited by 48
“Indeed, miR-210, by targeting both transcripts of the ISCU gene (ISCU1 and ISCU2, Iron-Sulfur Cluster Assembly Enzyme), represses the assembly of iron-sulfur clusters (Fe-S) that are present in several components of the electron transport chain and of the tricarboxylic acid cycle (22, 44, 46, 161).”
InfluentialInterplay Between Metabolism and Oncogenic Process: Role of microRNAs
Arora, A., Singh, S. P., Bhatt, A. N., Pandey, S., Sandhir, R., & Dwarakanath, B. S. R. (2015) · Translational Oncogenomics · doi:10.4137/tog.s29652 · Cited by 43
Influence of statins on distinct circulating microRNAs during prolonged aerobic exercise
Min, P., Park, J., Isaacs, S. K., Taylor, B. A., Thompson, P. D., Troyanos, C., d’Hemecourt, P. A., Dyer, S., Chan, S. Y., & Baggish, A. L. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00654.2015 · Cited by 44
“In parallel, RNA was extracted from cultured C2C12 myotubes as previously described (7) by the RNeasy Mini kit (Qiagen, Valencia, CA).”
MethodSelf-citationAerbajinai, W., Ghosh, M. C., Liu, J., Kumkhaek, C., Zhu, J., Chin, K., Rouault, T. A., & Rodgers, G. P. (2019) · Blood Advances · doi:10.1182/bloodadvances.2018026070 · Cited by 43
Telomeres, Aging and Exercise: Guilty by Association?
Chilton, W., O’Brien, B. J., & Charchar, F. J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122573 · Cited by 44
Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia
Liu, Y., Wang, M., Liang, Y., Wang, C., Naruse, K., & Takahashi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041729 · Cited by 42
“When the ISCU gene is inhibited, the mitochondrial metabolism decreases [125].”
BackgroundMitochondrial epigenetics in aging and cardiovascular diseases
Mongelli, A., Mengozzi, A., Geiger, M. A., Gorica, E., Mohammed, S. A., Paneni, F., Ruschitzka, F. T., & Costantino, S. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1204483 · Cited by 42
Exercise, Skeletal Muscle and Circulating microRNAs
Russell, A. P., & Lamon, S. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.018 · Cited by 43
Tsang, V., Dwight, T., Benn, D. E., Meyer-Rochow, G. Y., Gill, A. J., Sywak, M. S., Sidhu, S., Veivers, D., Sue, C. M., Robinson, B. G., et al. (2014) · Endocrine Related Cancer · doi:10.1530/erc-13-0519 · Cited by 42
“426 McCormick RI, Blick C, Ragoussis J, Schoedel J, Mole DR, Young AC, Selby PJ, Banks RE & Harris AL 2013 miR-210 is a target of hypoxiainducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.”
BackgroundInfluentialHypoxia-inducible factor-1 alpha as a therapeutic target for primary effusion lymphoma
Shrestha, P., Davis, D. A., Veeranna, R. P., Carey, R. F., Viollet, C., & Yarchoan, R. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006628 · Cited by 41
Endothelial Cell Mechano-Metabolomic Coupling to Disease States in the Lung Microvasculature
Wu, D., & Birukov, K. G. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00172 · Cited by 46
“This causes reduced mitochondrial respiration (decreased aconitase and Complex I activity) (Chan et al., 2009).”
BackgroundCompetition and collaboration between RNA ‐binding proteins and microRNAs
Ho, J. J. D., & Marsden, P. A. (2013) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1197 · Cited by 43
δ-Opioid Receptors, microRNAs, and Neuroinflammation in Cerebral Ischemia/Hypoxia
Chen, Y., He, X., Wang, S., & Xia, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00421 · Cited by 42
Li, Q., Liu, M., Sun, Y., Jin, T., Zhu, P., Wan, X., Hou, Y., & Tu, G. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01933-7 · Cited by 40
“It has been reported that hypoxia induces repression of complex I and III activity to reduce ROS production via miR-210/ISCU1/2 axis, leading to inhibition of apoptosis during hypoxic stress [10], suggesting that the adaptive modulation of mitochon-”
Background
Metadata
- Authors
- Chan, S. Y., Zhang, Y.-Y., Hemann, C., Mahoney, C. E., Zweier, J. L., & Loscalzo, J.
- Affiliations
- Harvard University (US)
- The Ohio State University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Loscalzo, Joseph
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 10
- Issue
- 4
- Pages
- 273-284
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2759401
- OpenAlex
- W2087408461
- Cited by
- 702
- References
- 37
- Citations by year
- 2026: 33 · 2025: 44 · 2024: 30 · 2023: 24 · 2022: 45 · 2021: 73 · 2020: 44 · 2019: 50 · 2018: 29 · 2017: 51 · 2016: 35 · 2015: 38 · 2014: 59 · 2013: 60 · 2012: 39
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hv28178-12-0-0)
- U.S. Public Health Service (P01 81587)
- National Heart, Lung, and Blood Institute (HL61795, K08HL096834, U54HL070819, P01HL081587, N01-HV-028178, R21HL089734, R01HL061795, R37HL061795)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Keywords
- miR-210, iron-sulfur cluster assembly, hypoxia, mitochondrial metabolism, mitochondrial respiration, pulmonary artery endothelial cells, complex I, aconitase, iron-sulfur proteins
- MeSH terms
- Animals, Hypoxia, Cells, Cultured, Gene Expression Regulation, Humans, Iron-Sulfur Proteins, Mitochondria, Oxygen Consumption, Mice, Knockout, MicroRNAs, Endothelial Cells, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Caspase 3, Caspase 7
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
