2016
DOI: 10.1073/pnas.1609865113
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Regulation of intracellular heme trafficking revealed by subcellular reporters

Abstract: Heme is an essential prosthetic group in proteins that reside in virtually every subcellular compartment performing diverse biological functions. Irrespective of whether heme is synthesized in the mitochondria or imported from the environment, this hydrophobic and potentially toxic metalloporphyrin has to be trafficked across membrane barriers, a concept heretofore poorly understood. Here we show, using subcellular-targeted, genetically encoded hemoprotein peroxidase reporters, that both extracellular and endo… Show more

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Cited by 109 publications
(138 citation statements)
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“…However, these approaches are less sensitive, as compared to the ones we describe herein, and moreover do not allow discriminating what proportion of the labile heme becomes bioavailable, which is made possible in our study based on the use of a cellular-based heme reporter assay [31,62]. …”
Section: Discussionmentioning
confidence: 99%
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“…However, these approaches are less sensitive, as compared to the ones we describe herein, and moreover do not allow discriminating what proportion of the labile heme becomes bioavailable, which is made possible in our study based on the use of a cellular-based heme reporter assay [31,62]. …”
Section: Discussionmentioning
confidence: 99%
“…Expression of HRP was confined to the Golgi with a targeting sequence from galactosyltransferase [12,31]. Control HEK293 cells were transiently transfected with the pEF5/FRT/V5-DEST vector [12,31]. Transfected cells were cultured (24 h) in DMEM (10% heme-depleted FBS) with or without succinylacetone (SA; 0.5 m m ) to block endogenous heme synthesis.…”
Section: Methodsmentioning
confidence: 99%
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“…Other known extracellular plasma HBPs are α1-microglobulin (Allhorn et al, 2002) and α1-antitrypsin (Karnaukhova et al, 2012) (Table 1). Intracellular binding of heme by HBPs may not only protect against its potential pro-oxidant toxicity, but may be also involved in trafficking of heme between different cell compartments (Muller Eberhard and Nikkilä, 1989; Liem et al, 1994; Yuan et al, 2016). Thus, the specific functional roles of intracellular candidate HBPs in mammalians such as glutathione-S-transferases, heme-binding protein/ liver fatty-acid binding protein, heme-binding protein 23/peroxiredoxin 1, p22 heme binding protein and glyceraldehyde-3-phosphate dehydrogenase (Harvey and Beutler, 1982; Vincent and Muller Eberhard, 1985; Iwahara et al, 1995; Taketani et al, 1998; Chakravarti et al, 2010) need to be investigated in more detail (Table 1).…”
Section: Protection Against Heme Toxicity Via Hemopexin and The Heme mentioning
confidence: 99%