ABCB6, an ABC Transporter Impacting Drug Response and Disease

Abstract

Recent findings have discovered how insufficiency of ATP-binding cassette (ABC) transporter, ABCB6 can negatively impact human health. These advances were made possible by, first finding that ABCB6 deficiency was the genetic basis for some severe transfusion reactions and second, by determining that functionally impaired ABCB6 variants enhanced the severity of porphyria, i.e., diseases associated with defects in heme synthesis. ABCB6 is a broad-spectrum porphyrin transporter that is capable of both exporting and importing heme and its precursors across the plasma membrane, and outer mitochondrial membrane, respectively. Biochemical studies have demonstrated that while ABCB6 influences the antioxidant system by reducing the levels of reactive oxygen species, the exact mechanism is currently unknown, though effects on heme synthesis are likely. Furthermore, it is unknown what biochemical or cellular signals determine where ABCB6 localizes in the cell. This review highlights the major recent findings on ABCB6 and focuses on details of its structure, mechanism, transport, contributions to cellular stress and current clinical implications.

The impact of cigarette smoke exposure, and COPD or asthma status on ABC transporter gene expression in human airway epithelial cells

“…ABCB6 over-expression increases catalase gene expression and stability 28 and is able to inhibit arsenic cytotoxicity 29 , a carcinogenic component found in cigarette smoke 30 . Despite the potential protective consequences of elevated ABCB6 expression that we observe in cigarette smokers, it is important to note that negative consequences may also arise as elevated ABCB6 levels may lead to resistance to chemotherapeutic agents 31 . Therefore, the observed up-regulation in ABCB6 is likely an important initial protective response to cigarette smoke exposure that may have untoward consequences of reducing responsiveness to chemotherapeutic agents for management of lung cancers.…”

Iron metabolic pathways in the processes of sponge plasticity

“…The Fe3+ ions are stored in association with FTH1 (ferritin) [67]. The porphyrins, including protoporphyrin IX (PpIX), are transported into mitochondria by the transport protein ABCB6 [68,69]. The transporter ABCG2 exports PpIX from mitochondria to the cytosol [70][71][72].…”

The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

“…And the diagnostic models integrating the four genes were useful for the early diagnosis of HCC with high speci city and sensitivity. ABCB6 belongs to the B subfamily of ABC transporters, which is a porphyrin energy-dependent transporter [50]. Gene expression analysis and animal experiments show that loss of Abcb6 can cause upregulation of heme and iron pathways crucial for normal development [51].…”