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Regulation of mitochondrial iron homeostasis by sideroflexin 2.

Authors :
Mon, Ei Ei
Wei, Fan-Yan
Ahmad, Raja Norazireen Raja
Yamamoto, Takahiro
Moroishi, Toshiro
Tomizawa, Kazuhito
Source :
Journal of Physiological Sciences; Mar2019, Vol. 69 Issue 2, p359-373, 15p
Publication Year :
2019

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
18806546
Volume :
69
Issue :
2
Database :
Complementary Index
Journal :
Journal of Physiological Sciences
Publication Type :
Academic Journal
Accession number :
134695051
Full Text :
https://doi.org/10.1007/s12576-018-0652-2