Department of Animal and Avian Sciences, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20740, United States of America.
School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States of America.
Biochim Biophys Acta Mol Cell Res. 2021 Jan;1868(1):118881. doi: 10.1016/j.bbamcr.2020.118881. Epub 2020 Oct 3.
Heme, as a hydrophobic iron-containing organic ring, is lipid soluble and can interact with biological membranes. The very same properties of heme that nature exploits to support life also renders heme potentially cytotoxic. In order to utilize heme, while also mitigating its toxicity, cells are challenged to tightly control the concentration and bioavailability of heme. On the bright side, it is reasonable to envision that, analogous to other transition metals, a combination of membrane-bound transporters, soluble carriers, and chaperones coordinate heme trafficking to subcellular compartments. However, given the dual properties exhibited by heme as a transition metal and lipid, it is compelling to consider the dark side: the potential role of non-proteinaceous biomolecules including lipids and nucleic acids that bind, sequester, and control heme trafficking and bioavailability. The emergence of inter-organellar membrane contact sites, as well as intracellular vesicles derived from various organelles, have raised the prospect that heme can be trafficked through hydrophobic channels. In this review, we aim to focus on heme delivery without deliverers - an alternate paradigm for the regulation of heme homeostasis through chaperone-less pathways for heme trafficking.
血红素作为一种疏水性含铁有机环，脂溶性，可以与生物膜相互作用。血红素在支持生命方面所利用的性质，也使其具有潜在的细胞毒性。为了利用血红素，同时减轻其毒性，细胞面临着严格控制血红素浓度和生物利用度的挑战。从好的方面来看，可以合理地设想，类似于其他过渡金属，膜结合转运蛋白、可溶性载体和伴侣蛋白的组合可以协调血红素向亚细胞区室的运输。然而，鉴于血红素作为过渡金属和脂质所表现出的双重特性，令人信服的是要考虑到黑暗面：非蛋白生物分子（包括脂质和核酸）的潜在作用，这些分子可以结合、隔离和控制血红素的运输和生物利用度。细胞器间膜接触位点的出现以及各种细胞器衍生的细胞内囊泡，使血红素可以通过疏水性通道运输成为可能。在这篇综述中，我们旨在关注无载体的血红素传递——通过无伴侣蛋白的血红素运输途径来调节血红素动态平衡的替代范例。
