Mitochondrial calcium trafficking plays an important role in human health, and its dysregulation has been implicated in a wide range of pathological conditions [1]. In particular, mitochondrial calcium overload causes cell death. In this presentation, we will discuss our development of mitochondrial calcium uptake inhibitors, as both potential therapeutic agents for treating mitochondria-related disorders and tools for studying the role of calcium trafficking in this organelle [2]. Our research in this area has shown that both ruthenium and cobalt coordination complexes can act as potent inhibitors of mitochondrial calcium uptake [3, 4]. Furthermore, proper tuning of the properties of these complexes can lead to effective inhibitors that operate in intact cell systems and can be leveraged for eliciting cytoprotective effects. This work demonstrates the potential of simple coordination complexes as ion channel inhibitors with therapeutic potential.

[1]  D. De Stefani, R. Rizzuto, T. Pozzan, Ann. Rev. Biochem., 2016, 85, 161-192.
[2]  J. J. Woods, J. J. Wilson, Curr. Opin. Chem. Biol., 2020, 55, 9-18.
[3]  J. J. Woods, N. Nemani, S. Shanmughapriya, A. Kumar, M. Zhang, S. R. Nathan, M. Thomas, E. Carvalho, K. Ramachandran, S. Srikantan, P. B. Stathopulos, J. J. Wilson, M. Madesh, ACS Cent. Sci., 2019, 5, 153-166.
[4]  J. J. Woods, M. X. Rodriguez, C.-W. Tsai, M.-F. Tsai, J. J. Wilson, Chem. Commun., 2021, doi: 10.1039/D1CC01623G