Control of bacterial second messenger signaling and motility by heme-based direct oxygen-sensing proteins

Hoque, Nushrat J; Weinert, Emily E

doi:10.1016/j.mib.2023.102396

Cited by 5 publications

(1 citation statement)

References 63 publications

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“…Ferrous iron (Fe 2+ )-bound protoporphyrin IX (PPIX) or heme b (thereon, referred to as heme) stands out as a metalated porphyrin with biochemical and physiological activities that go beyond oxygen transport, oxygen storage, electron transfer and catalysis [20]. Heme-bound proteins act as heme-responsive sensors and regulate transcription [20–24], microRNA splicing and processing [25], translation [26], heme degradation [27], protein degradation [28, 29], K + channel function [30], redox status [30–32] and protein-protein interactions [20]. The enzyme-catalyzed chelation of Fe 2+ in PPIX corresponds to the terminal step of the heme biosynthetic pathway [33–35].…”

Section: Introductionmentioning

confidence: 99%

Uncovering porphyrin accumulation in the tumor microenvironment

Adapa,

Sami,

Meshram

et al. 2024

Preprint

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Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be exquisitely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termedPorphyrin Overdrive. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME's stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention.

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