Kinase signaling adaptation supports dysfunctional mitochondria in disease

Skalka, G. L., Tsakovska, M. and Murphy, D. (2024) Kinase signaling adaptation supports dysfunctional mitochondria in disease. Frontiers in Molecular Biosciences, 11, 1354682. (doi: 10.3389/fmolb.2024.1354682)

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Mitochondria form a critical control nexus which are essential for maintaining correct tissue homeostasis. An increasing number of studies have identified dysregulation of mitochondria as a driver in cancer. However, which pathways support and promote this adapted mitochondrial function? A key hallmark of cancer is perturbation of kinase signalling pathways. These pathways include mitogen activated protein kinases (MAPK), lipid secondary messenger networks, cyclic-AMP-activated (cAMP)/ AMP-activated kinases (AMPK), and Ca2+/calmodulin-dependent protein kinase (CaMK) networks. These signalling pathways have multiple substrates which support initiation and persistence of cancer. Many of these are involved in the regulation of mitochondrial morphology, mitochondrial apoptosis, mitochondrial calcium homeostasis, mitochondrial associated membranes (MAMs), and retrograde ROS signalling. This review will aim to both explore how kinase signalling integrates with these critical mitochondrial pathways and highlight how these systems can be usurped to support the development of disease. In addition, we will identify areas which require further investigation to fully understand the complexities of these regulatory interactions. Overall, this review will emphasize how studying the interaction between kinase signalling and mitochondria improves our understanding of mitochondrial homeostasis and can yield novel therapeutic targets to treat disease.

Item Type:Articles
Additional Information:Funding was provided by the University of Glasgow and the CRUK Beaton Institute. GS was funded by Merck. DM is funded by CRUK (DRCNPG-Jun22\100007 and EDDPGM-Nov21\100001); MRC National mouse Genetics network cancer Cluster (315691-01); Asthma + Lung UK (MEDPG21F\5).
Glasgow Author(s) Enlighten ID:Skalka, Dr George and Murphy, Professor Daniel
Authors: Skalka, G. L., Tsakovska, M., and Murphy, D.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Frontiers in Molecular Biosciences
Publisher:Frontiers Media
ISSN (Online):2296-889X
Copyright Holders:Copyright © 2024 The Authors
First Published:First published in Frontiers in Molecular Biosciences 11:1354682
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
164008Using the Drosophila fly intestine to investigate Wnt targets in vivo.Owen SansomNational Centre for the Replacement of Animals Research (NC3RS)G1000078SCS - Beatson Institute for Cancer Research
315764Integrated analysis from mouse to man for Early detection of Mesothelioma.Daniel MurphyCancer Research UK (CRUK)EDDPGM-Nov21\100001SCS - Beatson Institute for Cancer Research