Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila

Taoka, H.; Murakawa, T.; Kawaguchi, K.; Koizumi, M.; Kaminishi, T.; Sakamaki, Y.; Tanaka, K.; Harada, A.; Inoue, K.; Kanki, T.; Ohkawa, Y.; Fujita, N.

doi:10.1101/2024.12.30.630714

bioRxiv · 10.1101/2024.12.30.630714

Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila

Taoka, H.·Murakawa, T.·Kawaguchi, K.·Koizumi, M.·Kaminishi, T.·Sakamaki, Y.·Tanaka, K.·Harada, A.·Inoue, K.·Kanki, T.·Ohkawa, Y.·Fujita, N.

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Abstract

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 (LIR) motif and minimal essential region (MER), 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. Impact statementA time-course RNA-seq analysis of muscle remodeling reveals transcriptional dynamics independent of autophagy and highlights the significance of BNIP3 in mitochondrial degradation in vivo.

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Taoka, H., Murakawa, T., Kawaguchi, K., Koizumi, M., Kaminishi, T., Sakamaki, Y., Tanaka, K., Harada, A., Inoue, K., Kanki, T., Ohkawa, Y., Fujita, N.. 2024-12-30. Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila. https://doi.org/10.1101/2024.12.30.630714

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