Journal Article

Identification of evolutionarily conserved regulators of muscle mitochondrial network organization

Ajayi, Peter T., Glancy, Brian, Bleck, Christopher K. E., Aponte, Angel, Katti, Prasanna

2022

Overview

Mitochondrial networks provide coordinated energy distribution throughout muscle cells. However, pathways specifying mitochondrial networks are incompletely understood and it is unclear how they might affect contractile fiber-type. 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 differentially. 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 through evolutionarily conserved transcription factors cut , salm , and H15 . Mitochondrial networks are carefully positioned to facilitate energy distribution within muscle cells. Here they show that energetic demands and conserved transcription factors regulate mitochondrial network organization and contractile phenotypes independently in Drosophila.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/19 / 14/28 / 14/34 / 14/35 / 38/77 / 38/89 / 631/136/2060/2068 / 631/443/319/333/1465 / 631/80/642/333/1465 / 64/24 / 82/58 / 82/80 / Animals / Configurations / Drosophila melanogaster - genetics / Drosophila melanogaster - metabolism / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Energy distribution / Flight muscle / Fruit flies / Humanities and Social Sciences / Insects / Leg / Legs / Mitochondria / multidisciplinary / Muscle contraction / Muscle, Skeletal - metabolism / Muscles / Networks / Osmosis / Phenotypes / Proteomics / Science / Science (multidisciplinary) / T-Box Domain Proteins - metabolism / Transcription factors / Transcription Factors - genetics / Transcription Factors - metabolism