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Molecular mechanisms of drug-mediate mitochondrial toxicity in renal tissues

Dr Amrita Mukherjee

Cells of the kidney tubules are packed with mitochondria and play a crucial role in the removal of toxins, making these cells vulnerable to mitochondrial damage. This can result in acute kidney injury and chronic kidney disease. The research project will investigate molecular pathways of drug-mediated mitochondrial toxicity in cultured proximal renal tubule cells and explore the recovery of renal tubule cells post-toxic injury in cultured 3D mini kidney organ systems, in the context of mitochondrial function.

We are interested in understanding the molecular mechanisms of mitochondrial toxicity with a particular emphasis on the proximal renal tubule cells. Toxins either ingested in the form of drugs or in food/drink are processed by the renal system and this makes them particularly vulnerable to toxin mediated damage. Using 2D and 3D cell culture systems we are looking at the effect of specific drugs on the renal tubule mitochondria. The molecular pathways uncovered will be validated in an in vivo model system like the Drosophila renal system. We are also interested to understand how renal cells recover after injury and will be using 3D kidney organoid systems to investigate this, all from the perspective of mitochondrial health.

 

Project members

Key publications

Popovic, R, Mukherjee, A, Santos Leal, N, Morris, L, Yu, Y, Loh, SHY, Martins LM. Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson’s disease. Cell Death & Disease 14, 206-215 (2023).

Mukherjee A, Pop S, Kondo S, Williams DW. RHG genes and mitochondria play a key non-apoptotic role in remodelling the Drosophila sensory system (bioRxiv 2021 DOI: https://doi.org/10.1101/2021.01.15.426850)

Mukherjee A, Conduit PT. γ-TuRCs are required for asymmetric microtubule nucleation from the somatic Golgi of Drosophila neurons (bioRxiv 2021 DOI: https://doi.org/10.1101/2021.09.24.461707)

 

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