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An Evolutionarily Conserved Regulatory Pathway of Muscle Mitochondrial Network Organization

Prasanna Katti, Peter T. Ajayi, Angel Aponte, View ORCID ProfileChristopher K.E. Bleck, Brian Glancy
doi: https://doi.org/10.1101/2021.09.30.462204
Prasanna Katti
1National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892, USA
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Peter T. Ajayi
1National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892, USA
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Angel Aponte
1National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892, USA
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Christopher K.E. Bleck
1National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892, USA
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  • ORCID record for Christopher K.E. Bleck
Brian Glancy
1National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD 20892, USA
2National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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  • For correspondence: brian.glancy@nih.gov
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Abstract

Mitochondrial networks provide coordinated energy distribution throughout muscle cells. However, pathways specifying mitochondrial network-type separately from contractile fiber-type remain unclear. Here, we show that natural energetic demands placed on Drosophila melanogaster muscles yield native cell-types among which contractile and mitochondrial network-types are regulated independently. Proteomic analyses of indirect flight, jump, and leg muscles together with muscles misexpressing known fiber-type specification factor salm identified transcription factors H15 and cut as potential mitochondrial network regulators. We demonstrate H15 operates downstream of salm regulating flight muscle contractile and mitochondrial network-type. Conversely, H15 regulates mitochondrial network configuration but not contractile type in jump and leg muscles. Further, we find that cut regulates salm expression in flight muscles and mitochondrial network configuration in leg muscles. These data indicate cell type-specific regulation of muscle mitochondrial network organization separately from contractile type, mitochondrial content, and mitochondrial size through an evolutionarily conserved pathway involving cut, salm, and H15.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted October 01, 2021.
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An Evolutionarily Conserved Regulatory Pathway of Muscle Mitochondrial Network Organization
Prasanna Katti, Peter T. Ajayi, Angel Aponte, Christopher K.E. Bleck, Brian Glancy
bioRxiv 2021.09.30.462204; doi: https://doi.org/10.1101/2021.09.30.462204
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An Evolutionarily Conserved Regulatory Pathway of Muscle Mitochondrial Network Organization
Prasanna Katti, Peter T. Ajayi, Angel Aponte, Christopher K.E. Bleck, Brian Glancy
bioRxiv 2021.09.30.462204; doi: https://doi.org/10.1101/2021.09.30.462204

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