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

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作者:Taoka Hiroki, Murakawa Tadayoshi, Kawaguchi Kohei, Koizumi Michiko, Kaminishi Tatsuya, Sakamaki Yuriko, Tanaka Kaori, Harada Akihito, Inoue Keiichi, Kanki Tomotake, Ohkawa Yasuyuki, Fujita Naonobu
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.

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