Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology

Kenta Onoue, Akihiro Jofuku, Reiko Ban-Ishihara, Takaya Ishihara, Maki Maeda, Takumi Koshiba, Takashi Itoh, Mitsunori Fukuda, Hidenori Otera, Toshihiko Oka, Hiroyoshi Takano, Noboru Mizushima, Katsuyoshi Mihara, Naotada Ishihara

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58 Citations (Scopus)

Abstract

In yeast, C-tail-anchored mitochondrial outer membrane protein Fis1 recruits the mitochondrial-fission-regulating GTPase Dnm1 to mitochondrial fission sites. However, the function of its mammalian homologue remains enigmatic because it has been reported to be dispensable for the mitochondrial recruitment of Drp1, a mammalian homologue of Dnm1. We identified TBC1D15 as a Fis1-binding protein in HeLa cell extracts. Immunoprecipitation revealed that Fis1 efficiently interacts with TBC1D15 but not with Drp1. Bacterially expressed Fis1 and TBC1D15 formed a direct and stable complex. Exogenously expressed TBC1D15 localized mainly in cytoplasm in HeLa cells, but when coexpressed with Fis1 it localized to mitochondria. Knockdown of TBC1D15 induced highly developed mitochondrial network structures similar to the effect of Fis1 knockdown, suggesting that the TBC1D15 and Fis1 are associated with the regulation of mitochondrial morphology independently of Drp1. These data suggest that Fis1 acts as a mitochondrial receptor in the recruitment of mitochondrial morphology protein in mammalian cells.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalJournal of cell science
Volume126
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Onoue, K., Jofuku, A., Ban-Ishihara, R., Ishihara, T., Maeda, M., Koshiba, T., Itoh, T., Fukuda, M., Otera, H., Oka, T., Takano, H., Mizushima, N., Mihara, K., & Ishihara, N. (2013). Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology. Journal of cell science, 126(1), 176-185. https://doi.org/10.1242/jcs.111211