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Updated: Aug 2, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Kinase perturbations redirect mitochondrial function in cancer
Omar Torres-Quesada1,2, Sophie Strich1, Eduard Stefan1,2
1Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria.
Abstract:
Protein kinases take the center stage in numerous signaling pathways by phosphorylating compartmentalized protein substrates for controlling cell proliferation, cell cycle and metabolism. Kinase dysfunctions have been linked to numerous human diseases such as cancer. This has led to the development of kinase inhibitors which aim to target oncogenic kinase activities. The specificity of the cancer blockers depends on the range of targeted kinases. Therefore, the question arises of how cell-type-specific off-target effects impair the specificities of cancer drugs. Blockade of kinase activities has been shown to converge on the energetic organelle, the mitochondria. In this review, we highlight examples of selected major kinases that impact mitochondrial signaling. Further, we discuss pharmacological strategies to target kinase activities linked to cancer progression and redirecting mitochondrial function. Finally, we propose that cell-based recordings of mitochondrial bioenergetic states might predict off-target or identify specific on-target effects of kinase inhibitors.
Insights
Protein kinases regulate cell processes, and their dysfunction causes cancer. Kinase inhibitors can have off-target effects on mitochondria, impacting cancer drug specificity. Mitochondrial bioenergetics may predict these effects.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein kinases are crucial in cell signaling, controlling proliferation, cell cycle, and metabolism.
- Dysfunctional kinases are implicated in diseases like cancer, leading to kinase inhibitor development.
- Kinase inhibitors' specificity is vital, but off-target effects can impair drug efficacy.
Purpose of the Study:
- To review major kinases affecting mitochondrial signaling.
- To discuss strategies for targeting kinase activities in cancer and mitochondrial function.
- To explore the potential of mitochondrial bioenergetics in predicting drug effects.
Main Methods:
- Literature review of kinase functions and mitochondrial signaling.
- Analysis of pharmacological strategies targeting kinases and mitochondria.
- Discussion of cell-based assays for monitoring mitochondrial bioenergetics.
Main Results:
- Selected major kinases significantly impact mitochondrial signaling pathways.
- Kinase inhibition can converge on mitochondria, affecting cellular energy.
- Pharmacological strategies aim to redirect mitochondrial function in cancer therapy.
Conclusions:
- Understanding kinase-mitochondria interactions is key for cancer drug development.
- Cell-based mitochondrial bioenergetic recordings can predict kinase inhibitor off-target effects.
- Targeting mitochondrial function offers a strategy to enhance cancer therapy specificity.
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