Regulation of mitochondrial iron homeostasis by sideroflexin 2

Mon, Ei Ei; Wei, Fan Yan; Ahmad, Raja Norazireen Raja; Yamamoto, Takahiro; Moroishi, Toshiro; Tomizawa, Kazuhito

doi:10.1007/s12576-018-0652-2

Cited by 39 publications

(44 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two recent publications shed light on the function of other sideroflexins: SFXN1 was found to be a serine transporter; however, SFXN4 did not compensate for the defects found in sideroflexin 1 mutants 35 . Sideroflexin 2, an outer mitochondrial membrane protein, has 20% sequence homology with SFXN4 and affects the iron content of mitochondria and heme synthesis, but has no effect on iron sulfur cluster formation 36 . Activity of respiratory complex one was also unchanged in a SFXN2 knockout 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Sideroflexin 2, an outer mitochondrial membrane protein, has 20% sequence homology with SFXN4 and affects the iron content of mitochondria and heme synthesis, but has no effect on iron sulfur cluster formation 36 . Activity of respiratory complex one was also unchanged in a SFXN2 knockout 36 . The function of SFXN4 therefore appears distinct from that of other SFXN family members studied to date.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes

Paul

Tesfay

Winkler

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Sideroflexin4 (SFXN4) is a member of a family of nuclear-encoded mitochondrial proteins. Rare germline mutations in SFXN4 lead to phenotypic characteristics of mitochondrial disease including impaired mitochondrial respiration and hematopoetic abnormalities. We sought to explore the function of this protein. We show that knockout of SFXN4 has profound effects on Fe-S cluster formation. This in turn diminishes mitochondrial respiratory chain complexes and mitochondrial respiration and causes a shift to glycolytic metabolism. SFXN4 knockdown reduces the stability and activity of cellular Fe-S proteins, affects iron metabolism by influencing the cytosolic aconitase–IRP1 switch, redistributes iron from the cytosol to mitochondria, and impacts heme synthesis by reducing levels of ferrochelatase and inhibiting translation of ALAS2. We conclude that SFXN4 is essential for normal functioning of mitochondria, is necessary for Fe-S cluster biogenesis and iron homeostasis, and plays a critical role in mitochondrial respiration and synthesis of heme.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes

Paul

Tesfay

Winkler

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Iron is an essential element involved in diverse biological processes, including oxygen transport, metabolism, respiration and cell cycle development (Zhang, 2014;Muckenthaler et al, 2017;Lv and Shang, 2018). A large portion of cellular iron is bound to heme that is used in a variety of proteins especially respiratory complexes, and cellular and mitochondrial iron concentrations are tightly regulated, including by various import/ export mechanisms (Napier et al, 2005;Kafina and Paw, 2017;Mon et al, 2019). Mitochondrial iron transporters, for example, DMT1 (MMT1), MRS3/4 and ABCB10 transport iron into mitochondria, whereas ABCB7 (Atm1) and ABCB8 (FXN), are mitochondrial iron efflux proteins (Mühlenhoff et al, 2003;Shaw et al, 2006;Chen et al, 2009;Zhao and Enns, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The increased in heme concentration can help account for the increased complex III and IV activities seen in ΔBbOhmm cells under LO conditions, since the two complexes contain heme (Alam et al, 2016). Mitochondrial iron is also indispensable for iron-sulfur (Fe-S) cluster assembly (Mon et al, 2019). Although no obvious change in mitochondrial iron levels was examined in either ΔBbOhmm or BbOhmm OE cells as compared to WT cells under AO condition, we cannot exclude the possibility that Fe-S cluster synthesis was altered in these cells.…”

Section: Discussionmentioning

confidence: 99%

The fungal mitochondrial membrane protein, BbOhmm, antagonistically controls hypoxia tolerance

Zhao

Gao

et al. 2020

Environmental Microbiology

View full text Add to dashboard Cite

Summary Adaptation to low‐oxygen (LO) environment in host tissues is crucial for microbial pathogens, particularly fungi, to successfully infect target hosts. However, the underlying mechanisms responsible for hypoxia tolerance in most pathogens are poorly understood. A mitochondrial protein, BbOhmm, is demonstrated to limit oxidative stress resistance and virulence in the insect fungal pathogen, Beauveria bassiana. Here, we found that BbOhmm negatively affected hypoxic adaptation in the insect haemocoel while regulating respiration‐related events, heme synthesis and mitochondrial iron homeostasis. A homologue of the mammalian sterol regulatory element‐binding proteins (SREBPs), BbSre1, was shown to be involved in BbOhmm‐mediated LO adaptation. Inactivation of BbSre1 resulted in a significant increase in sensitivity to hypoxic and oxidative stress. Similar to ΔBbOhmm, ΔBbSre1 or the ΔBbOhmmΔBbSre1 double mutant accumulated high levels of heme and mitochondrial iron, regulating the similar pathways during hypoxic stress. BbSre1 transcriptional activity and nuclear import were repressed in ΔBbOhmm cells and affected by intracellular reactive oxygen species (ROS) and oxygen levels. These findings have led to a new model in which BbOhmm affects ROS homeostasis in combination with available oxygen to control the transcriptional activity of BbSre1, which in turn mediates LO adaptation by regulating mitochondrial iron homeostasis, heme synthesis and respiration‐implicated genes.

show abstract

“…So far, no function has been described for UNC13B in cancer. SFXN2 , or sideroflexin 2 , is an evolutionary conserved protein that is expressed in outer mitochondrial membrane and is involved in iron homeostasis [ 29 ]. Similar to UNC13B , studies showing any functional correlation of SFXN2 with cancer progression, developments, etc.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis

Edemir

2020

IJMS

View full text Add to dashboard Cite

The information derived from next generation sequencing technology allows the identification of deregulated genes, gene mutations, epigenetic modifications, and other genomic events that are associated with a given tumor entity. Its combination with clinical data allows the prediction of patients’ survival with a specific gene expression pattern. Organic anion transporters and organic cation transporters are important proteins that transport a variety of substances across membranes. They are also able to transport drugs that are used for the treatment of cancer and could be used to improve treatment. In this study, we have made use of publicly available data to analyze if the expression of organic anion transporters or organic cation transporters have a prognostic value for a given tumor entity. The expression of most organic cation transporters is prognostic favorable. Within the organic anion transporters, the ratio between favorable and unfavorable organic anion transporters is nearly equal for most tumor entities and only in liver cancer is the number of unfavorable genes two times higher compared to favorable genes. Within the favorable genes, UNC13B, and SFXN2 cover nine cancer types and in the same way, SLC2A1, PLS3, SLC16A1, and SLC16A3 within the unfavorable set of genes and could serve as novel target structures.

show abstract

Regulation of mitochondrial iron homeostasis by sideroflexin 2

Cited by 39 publications

References 55 publications

Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes

Sideroflexin 4 affects Fe-S cluster biogenesis, iron metabolism, mitochondrial respiration and heme biosynthetic enzymes

The fungal mitochondrial membrane protein, BbOhmm, antagonistically controls hypoxia tolerance

Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis

Contact Info

Product

Resources

About