- The human MRS2 magnesium-binding domain is a regulatory feedback switch for channel activity S Uthayabalan, N Vishnu, M Madesh, PB Stathopulos. Life Science Alliance 6 (4)
- The mitochondrial regulation of smooth muscle cell proliferation in type 2 diabetes OM Koval, EK Nguyen, DJ Mittauer, K Ait-Aissa, W Chinchankar, L Qian, … bioRxiv
- Modulation of the mitochondrial Ca2+ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells A Patel, JG Pietromicca, M Venkatesan, S Maity, JE Bard, M Madesh, … Physiological Reports 11 (3), e15588
- The mitochondrial regulation of smooth muscle cell proliferation in type 2 diabetes IM Grumbach, OM Koval, E Nguyen, DJ Mittauer, K Ait-Aissa, … bioRxiv, 2023.02. 15.528765
- Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress. Madaris, T. R., Venkatesan, M., Maity, S., Stein, M. C., Vishnu, N., Venkateswaran, M. K., Davis, J. G., Ramachandran, K., Uthayabalan, S., Allen, C., Osidele, A., Stanley, K., Bigham, N. P., Bakewell, T. M., Narkunan, M., Le, A., Karanam, V., Li, K., Mhapankar, A., Norton, L., … Madesh, M. Cell reports, 42(3), 112155. Advance online publication.
Recent Publications
- A., Martinez-Sobrido, L., Yang, W., Stockand, J. D., Singh, B. B., Srikantan, S., … Madesh, M. (2022). SARS-CoV-2 infection enhances mitochondrial PTP complex activity to perturb cardiac energetics. iScience, 25(1), 103722. https://doi.org/10.1016/j.isci.2021.103722
- Ghosh, S., Zulkifli, M., Joshi, A., Venkatesan, M., Cristel, A., Vishnu, N., Madesh, M., & Gohil, V. M. (2022). MCU-complex-mediated mitochondrial calcium signaling is impaired in Barth syndrome. Human molecular genetics, 31(3), 376–385. https://doi.org/10.1093/hmg/ddab254
- Patel, A., Simkulet, M., Maity, S., Venkatesan, M., Matzavinos, A., Madesh, M., & Alevriadou, B. R. (2022). The mitochondrial Ca2+uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ Scientific reports, 12(1), 21161. https://doi.org/10.1038/s41598-022-25583-7
- Alevriadou, B. R., Patel, A., Noble, M., Ghosh, S., Gohil, V. M., Stathopulos, P. B., & Madesh, M. (2021). Molecular nature and physiological role of the mitochondrial calcium uniporter channel. American journal of physiology. Cell physiology, 320(4), C465–C482. https://doi.org/10.1152/ajpcell.00502.2020
- Lee, H. J., Donati, A., Feliers, D., Sun, Y., Ding, Y., Madesh, M., Salmon, A. B., Ikeno, Y., Ross, C., O’Connor, C. L., Ju, W., Bitzer, M., Chen, Y., Choudhury, G. G., Singh, B. B., Sharma, K., & Kasinath, B. S. (2021). Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury. Aging cell, 20(7), e13407. https://doi.org/10.1111/acel.13407
- Wetzel, M. D., Stanley, K., Maity, S., Madesh, M., Bopassa, J. C., & Awad, A. S. (2021). Homoarginine ameliorates diabetic nephropathy independent of nitric oxide synthase-3. Physiological reports, 9(5), e14766. https://doi.org/10.14814/phy2.14766
- Kerkhofs M., LaRovere, R., Welkenhuysen, K., Janssens,A., Vandenberghe,P., Muniswamy, M., Parys, J.B., Bultynck, G.(2021). BIRD-2, a BH4-domain-targeting peptide of Bcl-2, provokes Bax/Bak-independent cell death in B-cell cancers through mitochondrial Ca2+-dependent mPTP opening. Cell Calcium, 94, e102333. https://doi.org/10.1016/j.ceca.2020.102333
- Bekeschus, S., Eisenmann, S., Sagwal, S. K., Bodnar, Y., Moritz, J., Poschkamp, B., Stoffels, I., Emmert, S., Madesh, M., Weltmann, K. D., von Woedtke, T., & Gandhirajan, R. K. (2020). xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells. Redox biology, 30, 101423. https://doi.org/10.1016/j.redox.2019.101423
- Daw, C. C., Ramachandran, K., Enslow, B. T., Maity, S., Bursic, B., Novello, M. J., Rubannelsonkumar, C. S., Mashal, A. H., Ravichandran, J., Bakewell, T. M., Wang, W., Li, K., Madaris, T. R., Shannon, C. E., Norton, L., Kandala, S., Caplan, J., Srikantan, S., Stathopulos, P. B., Reeves, W. B., … Madesh, M. (2020). Lactate Elicits ER-Mitochondrial Mg2+Dynamics to Integrate Cellular Metabolism. Cell, 183(2), 474–489.e17. https://doi.org/10.1016/j.cell.2020.08.049
- Nemani, N., Dong, Z., Daw, C. C., Madaris, T. R., Ramachandran, K., Enslow, B. T., Rubannelsonkumar, C. S., Shanmughapriya, S., Mallireddigari, V., Maity, S., SinghMalla, P., Natarajanseenivasan, K., Hooper, R., Shannon, C. E., Tourtellotte, W. G., Singh, B. B., Reeves, W. B., Sharma, K., Norton, L., Srikantan, S., … Madesh, M. (2020). Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity. Science signaling, 13(628), eaaz6206. https://doi.org/10.1126/scisignal.aaz6206
- Tomar, D., Jaña, F., Dong, Z., Quinn, W. J., 3rd, Jadiya, P., Breves, S. L., Daw, C. C., Srikantan, S., Shanmughapriya, S., Nemani, N., Carvalho, E., Tripathi, A., Worth, A. M., Zhang, X., Razmpour, R., Seelam, A., Rhode, S., Mehta, A. V., Murray, M., Slade, D., … Madesh, M. (2019). Blockade of MCU-Mediated Ca2+Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation. Cell reports, 26(13), 3709–3725.e7. https://doi.org/10.1016/j.celrep.2019.02.107
- Lin, C. R., Bahmed, K., Tomar, D., Marchetti, N., Criner, G. J., Bolla, S., Wilson, M. A., Madesh, M., & Kosmider, B. (2019). The relationship between DJ-1 and S100A8 in human primary alveolar type II cells in emphysema. American journal of physiology. Lung cellular and molecular physiology, 317(6), L791–L804. https://doi.org/10.1152/ajplung.00494.2018
- Bahmed, K., Lin, C. R., Simborio, H., Karim, L., Aksoy, M., Kelsen, S., Tomar, D., Madesh, M., Elrod, J., Messier, E., Mason, R., Unterwald, E. M., Eisenstein, T. K., Criner, G. J., & Kosmider, B. (2019). The role of DJ-1 in human primary alveolar type II cell injury induced by e-cigarette aerosol. American journal of physiology. Lung cellular and molecular physiology, 317(4), L475–L485. https://doi.org/10.1152/ajplung.00567.2018
- Kalliora, C., Kyriazis, I. D., Oka, S. I., Lieu, M. J., Yue, Y., Area-Gomez, E., Pol, C. J., Tian, Y., Mizushima, W., Chin, A., Scerbo, D., Schulze, P. C., Civelek, M., Sadoshima, J., Madesh, M., Goldberg, I. J., & Drosatos, K. (2019). Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction. JCI insight, 5(17), e129556. https://doi.org/10.1172/jci.insight.129556
- Kosmider, B., Lin, C. R., Karim, L., Tomar, D., Vlasenko, L., Marchetti, N., Bolla, S., Madesh, M., Criner, G. J., & Bahmed, K. (2019). Mitochondrial dysfunction in human primary alveolar type II cells in emphysema. EBioMedicine, 46, 305–316. https://doi.org/10.1016/j.ebiom.2019.07.063
- Go, C. K., Hooper, R., Aronson, M. R., Schultz, B., Cangoz, T., Nemani, N., Zhang, Y., Madesh, M., & Soboloff, J. (2019). The Ca2+export pump PMCA clears near-membrane Ca2+ to facilitate store-operated Ca2+ entry and NFAT activation. Science signaling, 12(602), eaaw2627. https://doi.org/10.1126/scisignal.aaw2627
- Jaña, F., Bustos, G., Rivas, J., Cruz, P., Urra, F., Basualto-Alarcón, C., Sagredo, E., Ríos, M., Lovy, A., Dong, Z., Cerda, O., Madesh, M., & Cárdenas, C. (2019). Complex I and II are required for normal mitochondrial Ca2+Mitochondrion, 49, 73–82. https://doi.org/10.1016/j.mito.2019.07.004
- Nemani, N., Carvalho, E., Tomar, D., Dong, Z., Ketschek, A., Breves, S. L., Jaña, F., Worth, A. M., Heffler, J., Palaniappan, P., Tripathi, A., Subbiah, R., Riitano, M. F., Seelam, A., Manfred, T., Itoh, K., Meng, S., Sesaki, H., Craigen, W. J., Rajan, S., … Madesh, M. (2018). MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+Cell reports, 23(4), 1005–1019. https://doi.org/10.1016/j.celrep.2018.03.098
Discoveries
2010
Journal of Cell Biology
- STIM1 as a ROS sensor besides its canonical ER Ca2+ sensing role
2012 & 2013
Nature Cell Biology 2012
Highlights Nature Reviews
Molecular Cell Biology
- Demonstrated that a mitochondrial resident transmembrane protein Mitochondrial Ca2+ Uniporter Regulator 1 (MCUR1) is essential for Mitochondrial Ca2+ Uniporter (MCU)-mediated mitochondrial Ca2+ uptake.
Cell 2012 and Cell Reports 2013
- Identified the molecular component (Mitochondrial Ca2+ Uptake 1; MICU1) that controls mitochondrial Ca2+ uptake “set-point” a concept known over thirty years (Cell 2012 and Cell Reports 2013).
2015
Molecular Cell 2015
- Cell Reports- revealed that loss of MCU resulted in cell survival against hypoxia
- Molecular Cell- Identified a necessary and conserved role of spastic paraplegia 7 (SPG7). Our studies demonstrated that the IMM resident SPG7 promotes PTP opening, and the regulatory component CypD interacts with and activate SPG7 to induce death following Ca2+ and oxidative stress (Molecular Cell 2015)
Science Signaling 2015
- Dysregulation of mitochondrial Ca2+ uptake have been linked to numerous cellular dysfunction including chronic oxidative burden, autophagy and sensitization for cell death (Science Signaling 2015).
2016
Cell Reports 2016
- Deletion of MCU in vasculature offered perturbation of cell proliferation and migration.
Cell Chemical Biology 2016
- Our collaborative effort provided the first structural insights into the regulation of MCU and avenues to the development of MCU blockers that control the cell death.
- Demonstrated that a mitochondrial resident transmembrane protein Mitochondrial Ca2+ Uniporter Regulator 1 (MCUR1) is essential for Mitochondrial Ca2+ Uniporter (MCU)-mediated mitochondrial Ca2+ uptake
2017
Molecular Cell 2017 (preview)
Nature 2017
- Collaborative effort revealed the role of mitochondrial Na+/Ca2+ exchanger in Ca2+ homeostasis and cell viability
- Our discovery reveals for the first time the bifunctional role for MCU as an ion channel and mitochondrial ROS sensor.