Overview: ABC transporters and human disease

Area of Science:

• Biochemistry and Molecular Biology
• Genetics and Genomics
• Cell Biology

Background:

• ATP-binding cassette (ABC) transporters are a large superfamily found across all domains of life, characterized by conserved ATP-binding domains.
• These transporters utilize ATP hydrolysis to move substrates across cellular membranes, playing vital roles in cellular transport and regulation.
• While many ABC transporters function in substrate translocation, some are involved in regulating ion channels.

Purpose of the Study:

• To provide a comprehensive overview of the ABC transporter superfamily.
• To highlight the significance of ABC transporters in human health and disease.
• To discuss the role of ABC transporters in drug resistance.

Main Methods:

• Literature review and analysis of existing data on ABC transporter structure and function.
• Identification and categorization of known human ABC transporters and associated genetic diseases.
• Examination of the role of ABC transporters in substrate transport, including drugs.

Main Results:

• Approximately 1,100 ABC transporters are described globally, with about 50 identified in humans.
• Defects in 14 human ABC transporters are linked to 13 distinct genetic diseases, including cystic fibrosis and Stargardt disease.
• At least 8 ABC transporters handle amphipathic compounds, including anticancer drugs, and contribute to multidrug resistance in cancer cells.

Conclusions:

• ABC transporters are essential molecular machines with diverse functions across all life forms.
• Dysfunctional ABC transporters are implicated in a range of serious human genetic disorders.
• Targeting ABC transporters may offer strategies to overcome chemotherapy resistance in cancer treatment.