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Transcriptional dynamics uncover the role of BNIP3 in mitophagy during muscle remodeling in Drosophila.

Hiroki Taoka | Tadayoshi Murakawa | Kohei Kawaguchi | Michiko Koizumi | Tatsuya Kaminishi | Yuriko Sakamaki | Kaori Tanaka | Akihito Harada | Keiichi Inoue | Tomotake Kanki | Yasuyuki Ohkawa | Naonobu Fujita
eLife | 2025

Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due to the lack of a genetically trackable system. Previously, we reported that a subset of larval muscle cells is remodeled into adult abdominal muscle through an autophagy-dependent mechanism in Drosophila. To unveil the underlying mechanisms of this remodeling, we performed a comparative time-course RNA-seq analysis of isolated muscle cells with or without autophagy. It revealed both transcriptional dynamics independent of autophagy and highlighted the significance of BNIP3-mediated mitophagy in muscle remodeling. Mechanistically, we found that BNIP3 recruits autophagic machinery to mitochondria through its LC3-interacting motif and minimal essential region, which interact with Atg8a and Atg18a, respectively. Loss of BNIP3 leads to a substantial accumulation of larval mitochondria, ultimately impairing muscle remodeling. In summary, this study demonstrates that BNIP3-dependent mitophagy is critical for orchestrating the dynamic process of muscle remodeling.

Pubmed ID: 40801807

Additional research tools detected in this publication

Associated grants

  • Agency: Japan Society for the Promotion of Science,
    Id: 21H05147
  • Agency: Japan Science and Technology Agency,
    Id: 10.52926/JPMJPR18H8
  • Agency: Japan Agency for Medical Research and Development,
    Id: 24gm6410016h0001
  • Agency: Ministry of Education, Culture, Sports, Science, and Technology,
    Id: JPMXP1323015486

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Drosophila Genomics Resource Center (tool)

RRID:SCR_002845

Serves Drosophila research community by collecting and distributing DNA clones and vectors; collecting and distributing Drosophila cell lines; developing and testing genomics technologies for use in Drosophila and assisting members of the research community in their use.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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GFP Polyclonal Antibody : Trial Size (antibody)

RRID:AB_591816

This polyclonal targets GFP : Trial Size

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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w[*]; P{w[+mC]=UAS-Rheb.Pa}2 (organism)

RRID:BDSC_9688

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rheb.Pa}2 from BDSC.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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w[*]; P{w[+mC]=sqh-EYFP-Mito}3 (organism)

RRID:BDSC_7194

Drosophila melanogaster with name w[*]; P{w[+mC]=sqh-EYFP-Mito}3 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01937}attP2 (organism)

RRID:BDSC_25896

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01937}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00156}attP2 (organism)

RRID:BDSC_35578

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00156}attP2 from BDSC.

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w[1118]; P{y[+t7.7] w[+mC]=UAS-mito-QC}attP16 (organism)

RRID:BDSC_91640

Drosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=UAS-mito-QC}attP16 from BDSC.

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w[1118]; P{w[+mC]=UAS-mito-HA-GFP.AP}2/CyO (organism)

RRID:BDSC_8442

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-mito-HA-GFP.AP}2/CyO from BDSC.

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w[1118]; P{w[+mC]=UAS-lacZ.B}Bg4-1-2 (organism)

RRID:BDSC_1776

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-lacZ.B}Bg4-1-2 from BDSC.

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HISAT2 (software resource)

RRID:SCR_015530

Graph-based alignment of next generation sequencing reads to a population of genomes.

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pheatmap (software resource)

RRID:SCR_016418

Software tool as a function in R to draw clustered heatmaps for better control over graphical parameters.

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UMI-tools (software resource)

RRID:SCR_017048

Open source software package for handling Unique Molecular Identifiers in NGS data sets.

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DESeq2 (software resource)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01611}attP2/TM3, Sb[1] (organism)

RRID:BDSC_36918

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01611}attP2/TM3, Sb[1] from BDSC.

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Mfuzz (software resource)

RRID:SCR_000523

Software package for noise-robust soft clustering of gene expression time-series data (including a graphical user interface).

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PyMOL (software resource)

RRID:SCR_000305

A user-sponsored molecular visualization software system on an open-source foundation. The software has the capabilities to view, render, animate, export, present and develop three dimensional molecular structures.

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featureCounts (software resource)

RRID:SCR_012919

A read summarization program, which counts mapped reads for the genomic features such as genes and exons.

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w[1118]; P{w[+mC]=UAS-Dcr-2.D}10 (organism)

RRID:BDSC_24651

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Dcr-2.D}10 from BDSC.

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y[1] w[*]; P{w[+mC]=GAL4-Mef2.R}3 (organism)

RRID:BDSC_27390

Drosophila melanogaster with name y[1] w[*]; P{w[+mC]=GAL4-Mef2.R}3 from BDSC.

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