Mitochondrial fusion and altered beta-oxidation drive muscle wasting in a Drosophila cachexia model

Callum Dark; Nashia Ali; Sofya Golenkina; Vaibhav Dhyani; Ronnie Blazev; Benjamin L Parker; Kate T Murphy; Gordon S Lynch; Tarosi Senapati; S Sean Millard; Sarah M Judge; Andrew R Judge; Lopamudra Giri; Sarah M Russell; Louise Y Cheng

Journal article

Mitochondrial fusion and altered beta-oxidation drive muscle wasting in a Drosophila cachexia model

Callum Dark, Nashia Ali, Sofya Golenkina, Vaibhav Dhyani, Ronnie Blazev, Benjamin L Parker, Kate T Murphy, Gordon S Lynch, Tarosi Senapati, S Sean Millard, Sarah M Judge, Andrew R Judge, Lopamudra Giri, Sarah M Russell, Louise Y Cheng

EMBO Reports | Springer | Published : 2024

DOI: 10.1038/s44319-024-00102-z

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Abstract

Cancer cachexia is a tumour-induced wasting syndrome, characterised by extreme loss of skeletal muscle. Defective mitochondria can contribute to muscle wasting; however, the underlying mechanisms remain unclear. Using a Drosophila larval model of cancer cachexia, we observed enlarged and dysfunctional muscle mitochondria. Morphological changes were accompanied by upregulation of beta-oxidation proteins and depletion of muscle glycogen and lipid stores. Muscle lipid stores were also decreased in Colon-26 adenocarcinoma mouse muscle samples, and expression of the beta-oxidation gene CPT1A was negatively associated with muscle quality in cachectic patients. Mechanistically, mitochondrial defect..

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University of Melbourne Researchers

Callum Dark Author

Sofya Golenkina Author

Ronnie Blazev Author

Ben Parker Author

Related Projects (1)

IDENTIFICATION OF MEDIATORS OF CACHEXIA AND INTER-ORGAN CROSS-TALK IN DROSOPHILA

Cachexia is a metabolic disorder that affects some 9 million people worldwide, and involves extreme weight- and muscle-loss. It is a disease..

Grants

Awarded by DHAC | National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

We are grateful to Kieran Harvey, Donna Denton, Helena Richardson, Alex Gould, and Tatsushi Igaki for generous sharing of fly stocks and antibodies. We would like to thank Bloomington Drosophila Stock Center, Vienna Drosophila Resource Center and Developmental Studies Hybridoma Bank for fly stocks and antibodies. We would also like to thank OZDros for Drosophila quarantine, Peter MacCallum Cancer Institute Microscopy Core for technical assistance. We are grateful to Kellie Veen and Khanh Nguyen for assistance with illustrations, Yuchen Bai for technical assistance with mouse immunostaining experiments, Michelle Meier for assistance with mitochondrial quantifications and Daniel Bakopolous for intellectual input in this project. We would also like to thank Edel Alvarez and Khanh Nguyen for the critical reading of the manuscript. This work is funded by the NHMRC Ideas Grant APP1182847 and the Peter MacCallum Cancer Foundation.