MitoNEET Regulates Mitochondrial Iron Homeostasis Interacting with Transferrin Receptor

Takaaki Furihata, Shingo Takada, Satoshi Maekawa, Wataru Mizushima, Masashi Watanabe, Hidehisa Takahashi, Arata Fukushima, Masaya Tsuda, Junichi Matsumoto, Naoya Kakutani, Takashi Yokota, Shoji Matsushima, Yutaro Otsuka, Masaki Matsumoto, Keiichi I. Nakayama, Junko Nio-Kobayashi, Toshihoko Iwanaga, Hisataka Sabe, Shigetsugu Hatakeyama, Hiroyuki TsutsuiShintaro Kinugawa

Research output: Contribution to journalArticlepeer-review

Abstract

Iron is an essential trace element for regulation of redox and mitochondrial function, and then mitochondrial iron content is tightly regulated in mammals. We focused on a novel protein localized at the outer mitochondrial membrane. Immunoelectron microscopy revealed transferrin receptor (TfR) displayed an intimate relationship with the mitochondria, and mass spectrometry analysis also revealed mitoNEET interacted with TfR in vitro. Moreover, mitoNEET was endogenously coprecipitated with TfR in the heart, which indicates that mitoNEET also interacts with TfR in vivo. We generated mice with cardiac-specific deletion of mitoNEET (mitoNEET-knockout). Iron contents in isolated mitochondria were significantly increased in mitoNEET-knockout mice compared to control mice. Mitochondrial reactive oxygen species (ROS) were higher, and mitochondrial maximal capacity and reserve capacity were significantly decreased in mitoNEET-knockout mice, which was consistent with cardiac dysfunction evaluated by echocardiography. The complex formation of mitoNEET with TfR may regulate mitochondrial iron contents via an influx of iron. A disruption of mitoNEET could thus be involved in mitochondrial ROS production by iron overload in the heart.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - May 24 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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