Selected Publications

Shetty R, Noland R, Nandi G, Suzuki CK. Powering down the mitochondrial LonP1 protease: a novel strategy for anticancer therapeutics. Expert Opin Ther Targets. 2023 Dec 29:1-7. https://doi.org/10.1080/14728222.2023.2298358

Lail, N., Pandey, A.K., Venkatesh, S., Noland,R.D., Swanson, G., Pain, D., Branson, H., Suzuki, C.K., Yoon, G., Child Neurology: Progressive Cerebellar Atrophy and Retinal Dystrophy- Clues to an Ultra-Rare ACO2-Related Neurometabolic Diagnosis, Neurology, 101(15):e1567 (2023).

Li, Y., D. Huang, L. Jia, F. Shangguan, S. Gong, L. Lan, Z. Song, J. Xu, C. Yan, T. Chen, Y. Tan, Y. Liu, X. Huang, C.K. Suzuki, Z. Yang, G. Yang, and B. Lu. LonP1 Links Mitochondria-ER Interaction to Regulate Heart Function. Research (AAAS, Wash DC). 6:0175 (2023). Impact Factor of Research as per AAAS is 11.00 for 2022.

Lee, J., Pandey, A. K., Venkatesh, S., Thilagavathi, J., Honda, T., Singh, K., Suzuki, C.K. Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP – binding and -hydrolysis via CDDO and its derivatives. J. Biol. Chem. 298:101719 (2022).

Li, S., Li, W., Yuan, J., Bullova, P., Wu, J., Zhang, X., Liu, Y., Plescher, M., Rodriguez, J., Bedoya-Reina, O. C., Jannig, P. R., Valente-Silva, P., Yu, Meng, A. Henriksson, M., Zubarev, R. A., Sörensen, A. S., Suzuki, C.K., Ruas, J. L., Holmberg, J., Larsson, C., Juhlin, C. C., von Kriegsheim, A., Cao, Y., Schlisio, S. Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome. Nature Metabolism 4:739 (2022)

Venkatesh, S., Baljinnyam, E., Tong, M., Kashihara, T., Yan, L., Liu, T., Li, H., Xie, L.H., Nakamura, M., Oka, S., Suzuki, C.K., Fraidenraich, D., Sadoshima, J. Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cells. Am. J. Physiol.- Regulatory, Integrative and Comparative 320:R547-R562 (2020).

Lu, B., Shangguan, F., Huang, D., Gong, S., Shi, Y., Song, Z., Jia, L., Xu, J., Yan, Y., Chen, T., Xu, M., Li, Y., Han, S., Song, N., Chen, P., Wang, L., Liu, Y., Huang, X., Suzuki, C.K., Yang, Z., Yang, G. LonP1 Orchestrates UPRmt and UPRER and Mitochondrial Dynamics to Regulate Heart Function. bioRxiv 2019 doi: https://doi.org/10.1101/564492

Jeyapal, GP, Krishnasamy, R, Suzuki C.K., Venkatesh S, Chandrasekar MJN. In-silico design and synthesis of N9-substituted β-Carbolines as PLK-1 inhibitors and their in vitro/in-vivo tumor suppressing evaluation. Bioorganic Chemistry, 88:102913 (2019).

Venkatesh, S., Li, M., Saito, T., Rashed, E., Mareedu, S., Zhai, P., Bárcena, C., López-Otín, C., Yehia, G., Sadoshima, G., Suzuki, C.K. Mitochondrial LonP1 protects cardiomyocytes from ischemia/reperfusion injury in vivo. J. Mol. Cell, Cardio., 128:38 (2019).

Nimmo, G.A.M., Venkatesh, S., Pandey, A.K., Marshall, C.R., Hazrati, L.Z., Blaser, S., Ahmed, S., Cameron, J., Singh, K., Ray, P.N., Suzuki, C.K.*, Yoon, G.* Bi-allelic mutations of LONP1 encoding the mitochondrial LonP1 protease cause pyruvate dehydrogenase deficiency and profound neurodegeneration with progressive cerebellar atrophy. Hum. Mol. Gen., 28:290 (2019) **Co-Corresponding Authors

King, G.A., Shabestari, M.H., Taris, K.H., Pandey, A.K., Venkatesh, S., Thilagavathi, T., Singh, K., Koppisetti, R.K., Temiakov, D., Roos, W.H., Suzuki, C.K., Wuite, G.J.L., Acetylation and phosphorylation of human TFAM provide contrasting mechanisms for regulating non-specific TFAM-DNA interactions. Nucleic Acids Research, 46(7): 3633–3642 (2018).

Baljinnyam, E., Venkatesh, S., Gordan, R., Mareedu, S., Zhang, J., Xie, L-H, Azzam, EI, Suzuki, C.K., Fraidenraich, D. Effect of Densely Ionizing Radiation on Cardiomyocyte Differentiation from Human Induced Pluripotent Stem Cells. Physiological Reports, 5(15) e13308. doi: 10.14814/phy2.13308 (2017).

Sepuri, N.B., Angireddy, R., Srinivasan, S., Guha, M., Spear, J., Lu, B., Anandatheerthavarada, H.K., Suzuki, C.K., Avadhani, N. Mitochondrial LON Protease Dependent Degradation of Cytochrome c Oxidase Subunits under Hypoxia and Myocardial Ischemia. Biochimica et Biophysica Acta- Bioenergetics 1858(7):519-528 (2017).

Lan, L., Guo, M., Ai Y., Chen, F., Zhang, Y., Xia, L., Huang, D., Niu, L., Zheng, Y., Suzuki, C.K., Zhang, Y., Liu, Y., Lu, B. Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM. Bioscience Reports, 37(3) pii: BSR20170319 (2017).

Strauss, K.A., Jinks, R.N., Puffenberger, E.G. Venkatesh, S., Singh, K., Cheng, I., Mikita, N., Thilagavathi, J., Lee, J., Sarafianos, S., Benkert, A., Koehler, A., Zhu, A., Trovillion.V., McGlincy, M., Morlet, T., Deardorff, M., Innes, A.M., Prasad, C., Chudley, A.E., Lee, I.N.W., and Suzuki, C.K. CODAS syndrome is associated with mutations of LONP1 encoding mitochondrial AAA+ Lon protease. Am. J. Hum. Genet., 96, 121–135 (2015).

Lu, B., J. Lee, X. Nie, M. Li1, Y.I. Morozov, S. Venkatesh, D.F. Bogenhagen, D. Temiakov and C.K. Suzuki. Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Molecular Cell 49:121132 (2013).

Mitochondrial transcription factor A (TFAM) is essential for transcription of mitochondrial DNA (mtDNA), which specifically binds to promoter regions. TFAM also binds non-specifically to mtDNA leading to compaction of the genome. In this issue, Luet al. show that TFAM is phosphorylated at serine residues within its high mobility group box 1 (HMG1) by cAMP activated protein kinase (PKA).HMG1-phosphorylated TFAM and HMG1 phospho-mimics show defects in DNA-binding and transcriptional activation. Phospho-TFAM is rapidly degraded by the mitochondrial ATP-dependent LonP1 protease. Although much is known about how TFAM binds and compacts mtDNA, little is known about mechanisms regulating its release from the genome, which is crucial or replication, repair and transcription to proceed. These findings elucidate post-translational mechanisms for regulating the binding and release cycles of TFAM at the mitochondrial genome.
The illustration depicts TFAM (dendrobium orchids) either DNA-free or bound to mtDNA (green helix), which are phosphorylated by PKA (Hawaiian I’iwi). Phosphorylated and unphosphorylated dendrobiums are broken down into petals by the LonP1 protease (white spotted puffer fish). The different ratios of TFAM:mtDNA that have been reported to package the mitochondrial genome are shown as different styles of Hawaiian leis-the Moana Loa lei with the most densely packed orchids (bottom), and the classic double-and single-orchid leis (right and top, respectively). Illustration by Steve Haefele.

Chen S.H., C.K. Suzuki and S.H. Wu, Thermodynamic Characterization of Specific Interactions between Human Lon Protease andG-quartet DNA. Nucleic Acids Research, 36:1273-8 (2008).

Lu, N. Yadav,S., Shah,P.G.,Liu,T., Tian, B., Pukszta,S., Villaluna,N., Kutejová,E., Newlon,C.S., Santos, J.H., Suzuki, C.K.,Rolesfor the human ATP-dependent Lon protease in mitochondrial DNA maintenance. J. Biol. Chem 282:17363 (2007).

Liu, T., Lu, B., I. Lee, G. Ondrovicova, E. Kutejová and C.K. Suzuki. DNA and RNA binding by the mitochondrial Lon protease isregulated by nucleotide and protein substrate. J. Biol. Chem 279:13902 (2004).

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