2. Academic Validation
  3. Regulation of mitochondrial iron homeostasis by sideroflexin 2

Regulation of mitochondrial iron homeostasis by sideroflexin 2

  • J Physiol Sci. 2019 Mar;69(2):359-373. doi: 10.1007/s12576-018-0652-2.
Ei Ei Mon 1,  Fan-Yan Wei 2 3,  Raja Norazireen Raja Ahmad 1,  Takahiro Yamamoto 1,  Toshiro Moroishi 4 5 6,  Kazuhito Tomizawa 7 8 9
Affiliations

Affiliations

  • 1 Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-Ku, Kumamoto, 860-8556, Japan.
  • 2 Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-Ku, Kumamoto, 860-8556, Japan. [email protected].
  • 3 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, 332-0012, Japan. [email protected].
  • 4 Department of Molecular Enzymology, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • 5 Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
  • 6 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, 332-0012, Japan.
  • 7 Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Honjo 1-1-1, Chuo-Ku, Kumamoto, 860-8556, Japan. [email protected].
  • 8 Center for Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan. [email protected].
  • 9 Neutron Therapy Research Center, Okayama University, Okayama, 700-8558, Japan. [email protected].
PMID: 30570704 DOI: 10.1007/s12576-018-0652-2
Abstract

Mitochondrial iron is indispensable for heme biosynthesis and iron-sulfur cluster assembly. Several mitochondrial transmembrane proteins have been implicated to function in the biosynthesis of heme and iron-sulfur clusters by transporting reaction intermediates. However, several mitochondrial proteins related to iron metabolism remain uncharacterized. Here, we show that human sideroflexin 2 (SFXN2), a member of the SFXN protein family, is involved in mitochondrial iron metabolism. SFXN2 is an evolutionarily conserved protein that localized to mitochondria via its transmembrane domain. SFXN2-knockout (KO) cells had an increased mitochondrial iron content, which was associated with decreases in the heme content and heme-dependent Enzyme activities. By contrast, the activities of iron-sulfur cluster-dependent enzymes were unchanged in SFXN2-KO cells. Moreover, abnormal iron metabolism impaired mitochondrial respiration in SFXN2-KO cells and accelerated iron-mediated death of these cells. Our findings demonstrate that SFXN2 functions in mitochondrial iron metabolism by regulating heme biosynthesis.

Keywords

Heme; Iron; Mitochondria; OXPHOS; Respiration.

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