Higd1a is a positive regulator of cytochrome c oxidase

• DOI: 10.1073/pnas.1419767112
• Publication Date: 2015-01-21T06:19:22Z
• Authors: Takaharu Hayashi; Yoshihiro Asano; Yasunori Shintani; Hiroshi Aoyama; Hidetaka Kioka; Osamu Tsukamoto; Masahide Hikita; Kyoko Shinzawa-Itoh; Kazuaki Takafuji; Shuichiro Higo; Hisakazu Kato; Satoru Yamazaki; Ken Matsuoka; Atsushi Nakano; Hiroshi Asanuma; Masanori Asakura; Tetsuo Minamino; Yu-ichi Goto; Takashi Ogura; Masafumi Kitakaze; Issei Komuro; Yasushi Sakata; Tomitake Tsukihara; Shinya Yoshikawa; Seiji Takashima
• Keywords: 0301 basic medicine; Protein Conformation; Hypoxia-Inducible Factor 1, alpha Subunit; Oxidative Phosphorylation; Mitochondria; 3. Good health; Electron Transport Complex IV; 03 medical and health sciences; Adenosine Triphosphate; Fluorescence Resonance Energy Transfer; Animals; Cattle; Hypoxia

Significance

We identified hypoxia-inducible domain family, member 1A (Higd1a) as a positive regulator of cytochrome c oxidase (CcO). CcO, the terminal component of the mitochondrial electron transfer system, reductively converts molecular oxygen to water coupled to pump protons across the inner mitochondrial membrane. Higd1a is transiently induced under hypoxic conditions and increases CcO activity by directly interacting with CcO in the vicinity of its active center. Induction of Higd1a leads to increased oxygen consumption and subsequent mitochondrial ATP synthesis, thereby improving cell viability under hypoxia.