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.

血红素作为疏水性含铁有机环，具有脂溶性，可与生物膜相互作用。大自然用来支持生命的血红素的相同特性也使血红素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。从好的方面来说，可以合理地设想，与其他过渡金属类似，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表现出的双重特性，考虑到阴暗面是令人信服的：包括脂质和核酸在内的非蛋白质生物分子的潜在作用，它们结合、隔离、并控制血红素贩运和生物利用度。细胞器间膜接触位点的出现，以及来自各种细胞器的细胞内囊泡的出现，提高了血红素可以通过疏水通道运输的前景。在这篇综述中，我们的目标是关注没有递送者的血红素递送——通过无伴侣途径进行血红素贩运来调节血红素稳态的另一种范式。