Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology

Abstract

Kidneys have a high resting metabolic rate and low partial pressure of oxygen due to enhanced mitochondrial oxygen consumption and ATP production needed for active solute transport. Heightened mitochondrial activity leads to progressively increasing hypoxia from the renal cortex to the renal medulla. Renal hypoxia is prominent in hypertensive rats due to increased sodium reabsorption within the nephrons, which demands higher energy production by oxidative phosphorylation (OXPHOS). Consequently, spontaneously hypertensive rats (SHR) display greater oxygen deficiency (hypoxia) than normotensive Wistar Kyoto rats (WKY). Here, we sought to investigate the expression of key proteins for mitochondrial biogenesis in SHR and WKY, and study the regulation of mitochondrial transcription factors (mtTFs) under in vitro hypoxic conditions in renal epithelial cells. We report that renal expressions of hypoxia-inducible factor-1-alpha (HIF-1α), peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α), mtTFs, and OXPHOS proteins are elevated in SHR compared to WKY. In addition, our experiments in cultured kidney cells demonstrate that acute hypoxia augments the expression of these genes. Furthermore, we show that the transcripts of HIF-1α and mtTFs are positively correlated in various human tissues. We reveal, for the first time to our knowledge, that HIF-1α transactivates mtTF genes by direct interaction with their promoters in rat kidney epithelial cells (NRK-52E) under acute hypoxia. Concomitant increases in the mitochondrial DNA and RNA, and OXPHOS proteins are observed. Taken together, this study suggests that hypoxia within the renal epithelial cells may enhance mitochondrial function to meet the energy demand in proximal tubular cells during prehypertensive stages in kidneys of young SHR.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Levy MN. Effect of variations of blood flow on renal oxygen extraction. Am J Physiol. 1960;199:13–8.

    Article  CAS  PubMed  Google Scholar 

  2. Hansell P, Welch WJ, Blantz RC, Palm F. Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension. Clin Exp Pharm Physiol. 2013;40:123–37.

    Article  CAS  Google Scholar 

  3. Welch WJ, Baumgartl H, Lubbers D, Wilcox CS. Nephron pO2 and renal oxygen usage in the hypertensive rat kidney. Kidney Int. 2001;59:230–7.

    Article  CAS  PubMed  Google Scholar 

  4. Curthoys NP, Moe OW. Proximal tubule function and response to acidosis. Clin J Am Soc Nephrol. 2014;9:1627–38.

    Article  CAS  PubMed  Google Scholar 

  5. Palmer LG, Schnermann J. Integrated control of Na transport along the nephron. Clin J Am Soc Nephrol. 2015;10:676–87.

    Article  CAS  PubMed  Google Scholar 

  6. Layton AT, Vallon V, Edwards A. Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition. Am J Physiol Ren Physiol. 2015;308:F1343–57.

    Article  CAS  Google Scholar 

  7. Tuma Z, Kuncova J, Mares J, Matejovic M. Mitochondrial proteomes of porcine kidney cortex and medulla: foundation for translational proteomics. Clin Exp Nephrol. 2016;20:39–49.

    Article  CAS  PubMed  Google Scholar 

  8. Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med. 2015;21:37–46.

    Article  CAS  PubMed  Google Scholar 

  9. Debevec T, Millet GP, Pialoux V. Hypoxia-induced oxidative stress modulation with physical activity. Front Physiol. 2017;8:84.

    PubMed  PubMed Central  Google Scholar 

  10. O’Hagan KA, Cocchiglia S, Zhdanov AV, Tambuwala MM, Cummins EP, Monfared M, et al. PGC-1alpha is coupled to HIF-1alpha-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells. Proc Natl Acad Sci USA. 2009;106:2188–93.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Guyton AC. The surprising kidney-fluid mechanism for pressure control–its infinite gain! Hypertension. 1990;16:725–30.

    Article  CAS  PubMed  Google Scholar 

  12. Jaffe D, Sutherland LE, Barker DM, Dahl LK. Effects of chronic excess salt ingestion. Morphologic findings in kidneys of rats with differing genetic susceptibilities to hypertension. Arch Pathol. 1970;90:1–16.

    CAS  PubMed  Google Scholar 

  13. Chiolero A, Maillard M, Nussberger J, Brunner HR, Burnier M. Proximal sodium reabsorption: an independent determinant of blood pressure response to salt. Hypertension. 2000;36:631–7.

    Article  CAS  PubMed  Google Scholar 

  14. LaPointe MS, Sodhi C, Sahai A, Batlle D. Na+/H+ exchange activity and NHE-3 expression in renal tubules from the spontaneously hypertensive rat. Kidney Int. 2002;62:157–65.

    Article  CAS  PubMed  Google Scholar 

  15. Beach RE, DuBose TD Jr. Adrenergic regulation of (Na+, K+)-ATPase activity in proximal tubules of spontaneously hypertensive rats. Kidney Int. 1990;38:402–8.

    Article  CAS  PubMed  Google Scholar 

  16. Hatziioanou D, Barkas G, Critselis E, Zoidakis J, Gakiopoulou H, Androutsou ME, et al. Chloride intracellular channel 4 overexpression in the proximal tubules of kidneys from the spontaneously hypertensive rat: insight from proteomic analysis. Nephron. 2018;138:60–70.

    Article  CAS  PubMed  Google Scholar 

  17. Lewis JL, Warnock DG. Renal apical membrane sodium-hydrogen exchange in genetic salt-sensitive hypertension. Hypertension. 1994;24:491–8.

    Article  CAS  PubMed  Google Scholar 

  18. Liu J, Yan Y, Liu L, Xie Z, Malhotra D, Joe B, et al. Impairment of Na/K-ATPase signaling in renal proximal tubule contributes to Dahl salt-sensitive hypertension. J Biol Chem. 2011;286:22806–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. de Cavanagh EM, Toblli JE, Ferder L, Piotrkowski B, Stella I, Inserra F. Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1616–25.

    Article  PubMed  CAS  Google Scholar 

  20. Welch WJ, Baumgartl H, Lubbers D, Wilcox CS. Renal oxygenation defects in the spontaneously hypertensive rat: role of AT1 receptors. Kidney Int. 2003;63:202–8.

    Article  CAS  PubMed  Google Scholar 

  21. Gu Q, Zhao L, Ma YP, Liu JD. Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats. Mol Cell Biochem. 2015;406:217–25.

    Article  CAS  PubMed  Google Scholar 

  22. Lee H, Abe Y, Lee I, Shrivastav S, Crusan AP, Huttemann M, et al. Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats. Kidney Int. 2014;85:561–9.

    Article  CAS  PubMed  Google Scholar 

  23. Rettig R, Folberth CG, Graf C, Kopf D, Stauss H, Unger T. Are renal mechanisms involved in primary hypertension? Evidence from kidney transplantation studies in rats. Klin Wochenschr. 1991;69:597–602.

    Article  CAS  PubMed  Google Scholar 

  24. Rettig R. Does the kidney play a role in the aetiology of primary hypertension? Evidence from renal transplantation studies in rats and humans. J Hum Hypertens. 1993;7:177–80.

    CAS  PubMed  Google Scholar 

  25. Clayton DA. Transcription and replication of mitochondrial DNA. Hum Reprod. 2000;15(Suppl 2):11–7.

    Article  PubMed  Google Scholar 

  26. Rantanen A, Gaspari M, Falkenberg M, Gustafsson CM, Larsson NG. Characterization of the mouse genes for mitochondrial transcription factors B1 and B2. Mamm Genome. 2003;14:1–6.

    Article  CAS  PubMed  Google Scholar 

  27. Litonin D, Sologub M, Shi Y, Savkina M, Anikin M, Falkenberg M, et al. Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem. 2010;285:18129–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Metodiev MD, Lesko N, Park CB, Camara Y, Shi Y, Wibom R, et al. Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab. 2009;9:386–97.

    Article  CAS  PubMed  Google Scholar 

  29. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol. 2005;25:1354–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yang ZF, Drumea K, Mott S, Wang J, Rosmarin AG. GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis. Mol Cell Biol. 2014;34:3194–201.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Sandelin A, Wasserman WW, Lenhard B. ConSite: web-based prediction of regulatory elements using cross-species comparison. Nucleic Acids Res. 2004;32:W249–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Quandt K, Frech K, Karas H, Wingender E, Werner T. MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 1995;23:4878–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lee C, Huang CH. LASAGNA-Search: an integrated web tool for transcription factor binding site search and visualization. Biotechniques. 2013;54:141–53.

    Article  CAS  PubMed  Google Scholar 

  34. Fornes O, Castro-Mondragon JA, Khan A, van der Lee R, Zhang X, Richmond PA, et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2020;48:D87–92.

    Article  CAS  PubMed  Google Scholar 

  35. Chekmenev DS, Haid C, Kel AE. P-Match: transcription factor binding site search by combining patterns and weight matrices. Nucleic Acids Res. 2005;33:W432–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Arige V, Agarwal A, Khan AA, Kalyani A, Natarajan B, Gupta V, et al. Regulation of monoamine oxidase B gene expression: key roles for transcription factors Sp1, Egr1 and CREB, and microRNAs miR-300 and miR-1224. J Mol Biol. 2019;431:1127–47.

    Article  CAS  PubMed  Google Scholar 

  37. Koh JH, Johnson ML, Dasari S, LeBrasseur NK, Vuckovic I, Henderson GC, et al. TFAM enhances fat oxidation and attenuates high-fat diet-induced insulin resistance in skeletal muscle. Diabetes. 2019;68:1552–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhu L, Wang Q, Zhang L, Fang Z, Zhao F, Lv Z, et al. Hypoxia induces PGC-1alpha expression and mitochondrial biogenesis in the myocardium of TOF patients. Cell Res. 2010;20:676–87.

    Article  CAS  PubMed  Google Scholar 

  39. Friederich-Persson M, Thorn E, Hansell P, Nangaku M, Levin M, Palm F. Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress. Hypertension. 2013;62:914–9.

    Article  CAS  PubMed  Google Scholar 

  40. Liss P, Nygren A, Revsbech NP, Ulfendahl HR. Intrarenal oxygen tension measured by a modified clark electrode at normal and low blood pressure and after injection of x-ray contrast media. Pflug Arch. 1997;434:705–11.

    Article  CAS  Google Scholar 

  41. Consortium GT. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45:580–5.

    Article  CAS  Google Scholar 

  42. Lan R, Geng H, Singha PK, Saikumar P, Bottinger EP, Weinberg JM, et al. Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI. J Am Soc Nephrol. 2016;27:3356–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006;3:187–97.

    Article  CAS  PubMed  Google Scholar 

  44. Goodall S, Twomey R, Amann M. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance. Fatigue. 2014;2:73–92.

    PubMed  PubMed Central  Google Scholar 

  45. Reiterer M, Colaco R, Emrouznejad P, Jensen A, Rundqvist H, Johnson RS, et al. Acute and chronic hypoxia differentially predispose lungs for metastases. Sci Rep. 2019;9:10246.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Virbasius JV, Scarpulla RC. Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc Natl Acad Sci USA. 1994;91:1309–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450:736–40.

    Article  CAS  PubMed  Google Scholar 

  48. Zheng W, Zhao H, Mancera E, Steinmetz LM, Snyder M. Genetic analysis of variation in transcription factor binding in yeast. Nature. 2010;464:1187–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Schodel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood. 2011;117:e207–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Malarkey CS, Bestwick M, Kuhlwilm JE, Shadel GS, Churchill ME. Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA. Nucleic Acids Res. 2012;40:614–24.

    Article  CAS  PubMed  Google Scholar 

  51. Wang YE, Marinov GK, Wold BJ, Chan DC. Genome-wide analysis reveals coating of the mitochondrial genome by TFAM. PLoS ONE. 2013;8:e74513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Thomas JL, Pham H, Li Y, Hall E, Perkins GA, Ali SS, et al. Hypoxia-inducible factor-1alpha activation improves renal oxygenation and mitochondrial function in early chronic kidney disease. Am J Physiol Ren Physiol. 2017;313:F282–90.

    Article  CAS  Google Scholar 

  53. Galvan DL, Green NH, Danesh FR. The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney Int. 2017;92:1051–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang Z, Ying Z, Bosy-Westphal A, Zhang J, Schautz B, Later W, et al. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr. 2010;92:1369–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kuhlmann U, Schwickardi M, Trebst R, Lange H. Resting metabolic rate in chronic renal failure. J Ren Nutr. 2001;11:202–6.

    Article  CAS  PubMed  Google Scholar 

  56. Meyer C, Nadkarni V, Stumvoll M, Gerich J. Human kidney free fatty acid and glucose uptake: evidence for a renal glucose-fatty acid cycle. Am J Physiol. 1997;273:E650–4.

    CAS  PubMed  Google Scholar 

  57. Thomas D, Harris PJ, Morgan TO. Age-related changes in angiotensin II-stimulated proximal tubule fluid reabsorption in the spontaneously hypertensive rat. J Hypertens. 1988;6:S449–51.

    Article  CAS  Google Scholar 

  58. Aldred KL, Harris PJ, Eitle E. Increased proximal tubule NHE-3 and H+-ATPase activities in spontaneously hypertensive rats. J Hypertens. 2000;18:623–8.

    Article  CAS  PubMed  Google Scholar 

  59. Boer PA, Morelli JM, Figueiredo JF, Gontijo JA. Early altered renal sodium handling determined by lithium clearance in spontaneously hypertensive rats (SHR): role of renal nerves. Life Sci. 2005;76:1805–15.

    Article  CAS  PubMed  Google Scholar 

  60. Queiroz-Madeira EP, Lara LS, Wengert M, Landgraf SS, Libano-Soares JD, Zapata-Sudo G, et al. Na(+)-ATPase in spontaneous hypertensive rats: possible AT(1) receptor target in the development of hypertension. Biochim Biophys Acta. 2010;1798:360–6.

    Article  CAS  PubMed  Google Scholar 

  61. Hinojos CA, Doris PA. Altered subcellular distribution of Na+,K+-ATPase in proximal tubules in young spontaneously hypertensive rats. Hypertension. 2004;44:95–100.

    Article  CAS  PubMed  Google Scholar 

  62. Adler S, Huang H. Impaired regulation of renal oxygen consumption in spontaneously hypertensive rats. J Am Soc Nephrol. 2002;13:1788–94.

    Article  CAS  PubMed  Google Scholar 

  63. Heckmann U, Zidek W, Schurek HJ. Sodium reabsorption in the isolated perfused kidney of normotensive and spontaneously hypertensive rats. J Hypertens. 1989;7:S172–3.

    Article  CAS  Google Scholar 

  64. Li J, He Q, Wu W, Li Q, Huang R, Pan X, et al. Role of the renal sympathetic nerves in renal sodium/potassium handling and renal damage in spontaneously hypertensive rats. Exp Ther Med. 2016;12:2547–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Biollaz J, Waeber B, Diezi J, Burnier M, Brunner HR. Lithium infusion to study sodium handling in unanesthetized hypertensive rats. Hypertension. 1986;8:117–21.

    Article  CAS  PubMed  Google Scholar 

  66. Wu A, Wolley M, Stowasser M. The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway. J Hum Hypertens. 2019;7:508–23.

    Article  CAS  Google Scholar 

  67. Cowley AW Jr., Abe M, Mori T, O’Connor PM, Ohsaki Y, Zheleznova NN. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Am J Physiol Ren Physiol. 2015;308:F179–97.

    Article  CAS  Google Scholar 

  68. Chen Y, Jiang S, Zou J, Zhong Y, Ding X. Silencing HIF-1alpha aggravates growth inhibition and necrosis of proximal renal tubular epithelial cell under hypoxia. Ren Fail. 2016;38:1726–34.

    Article  CAS  PubMed  Google Scholar 

  69. Zhan CD, Sindhu RK, Pang J, Ehdaie A, Vaziri ND. Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. J Hypertens. 2004;22:2025–33.

    Article  CAS  PubMed  Google Scholar 

  70. Lacher SE, Levings DC, Freeman S, Slattery M. Identification of a functional antioxidant response element at the HIF1A locus. Redox Biol. 2018;19:401–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Nezu M, Souma T, Yu L, Suzuki T, Saigusa D, Ito S, et al. Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression. Kidney Int. 2017;91:387–401.

    Article  CAS  PubMed  Google Scholar 

  72. Noel S, Hamad AR, Rabb H. Reviving the promise of transcription factor Nrf2-based therapeutics for kidney diseases. Kidney Int. 2015;88:1217–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Li H, Satriano J, Thomas JL, Miyamoto S, Sharma K, Pastor-Soler NM, et al. Interactions between HIF-1alpha and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease. Am J Physiol Ren Physiol. 2015;309:F414–28.

    Article  CAS  Google Scholar 

  74. Simao S, Gomes P, Pinto V, Silva E, Amaral JS, Igreja B, et al. Age-related changes in renal expression of oxidant and antioxidant enzymes and oxidative stress markers in male SHR and WKY rats. Exp Gerontol. 2011;46:468–74.

    Article  CAS  PubMed  Google Scholar 

  75. Spelbrink JN. Functional organization of mammalian mitochondrial DNA in nucleoids: history, recent developments, and future challenges. IUBMB Life. 2010;62:19–32.

    CAS  PubMed  Google Scholar 

  76. Kukat C, Davies KM, Wurm CA, Spahr H, Bonekamp NA, Kuhl I, et al. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc Natl Acad Sci USA. 2015;112:11288–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ngo HB, Lovely GA, Phillips R, Chan DC. Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nat Commun. 2014;5:3077.

    Article  PubMed  CAS  Google Scholar 

  78. Pastukh VM, Gorodnya OM, Gillespie MN, Ruchko MV. Regulation of mitochondrial genome replication by hypoxia: the role of DNA oxidation in D-loop region. Free Radic Biol Med. 2016;96:78–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Vinogradov AD, Grivennikova VG. Oxidation of NADH and ROS production by respiratory complex I. Biochim Biophys Acta. 2016;1857:863–71.

    Article  CAS  PubMed  Google Scholar 

  80. Bleier L, Drose S. Superoxide generation by complex III: from mechanistic rationales to functional consequences. Biochim Biophys Acta. 2013;1827:1320–31.

    Article  CAS  PubMed  Google Scholar 

  81. Biswas SK, de Faria JB. Which comes first: renal inflammation or oxidative stress in spontaneously hypertensive rats? Free Radic Res. 2007;41:216–24.

    Article  CAS  PubMed  Google Scholar 

  82. Rodriguez-Iturbe B, Quiroz Y, Ferrebuz A, Parra G, Vaziri ND. Evolution of renal interstitial inflammation and NF-kappaB activation in spontaneously hypertensive rats. Am J Nephrol. 2004;24:587–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Various Government of India Research fellowships were received from the Council of Scientific and Industrial Research (BN), the Department of Science and Technology (VA), Ministry of Human Resource Development (AAK), and the Indian Council of Medical Research (SSR). The authors thank Manish Jain and Dr Madhu Dikshit, CSIR-Central Drug Research Institute, Lucknow, India, for their help at the initial phase of this study. The authors appreciate the valuable and timely help offered by V. Janani, Indian Institute of Technology Madras, Chennai, India.

Funding

This work was supported by a grant from the Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India, to NRM (project number EMR/2017/004250).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nitish R. Mahapatra.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Natarajan, B., Arige, V., Khan, A.A. et al. Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology. Hypertens Res 44, 154–167 (2021). https://doi.org/10.1038/s41440-020-00539-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-020-00539-4

Keywords

This article is cited by

Search

Quick links