Structural Mechanism of Transport of Mitochondrial Carriers

• Published in: Annual review of biochemistry Vol. 90; no. 1; pp. 535 - 558
• Main Authors: Ruprecht, J. J, Kunji, E.R.S
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 20-06-2021; Annual Reviews, Inc
• Subjects: ADP ATP carrier; Aggrecans - chemistry; Aggrecans - genetics; Aggrecans - metabolism; Amino Acid Sequence; Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Binding Sites; bioenergetics; Biological Transport; Calcium - metabolism; Carboxylic acids; Cardiolipins - metabolism; Chemical synthesis; Conserved Sequence; Cytoplasm - metabolism; Fatty acids; Homeostasis; Humans; Lipid metabolism; Lipids; Macromolecules; membrane protein dynamics; Membranes; Mitochondria; Mitochondrial ADP, ATP Translocases - chemistry; Mitochondrial ADP, ATP Translocases - metabolism; mitochondrial diseases; Mitochondrial Membrane Transport Proteins - chemistry; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; mitochondrial physiology; Mutation; Nucleotides; Oxidative phosphorylation; Phosphorylation; Protein Conformation; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Substrates; Sugar; uncoupling protein; Vitamins; mitochondrial physiology; mitochondrial diseases; bioenergetics; membrane protein dynamics; ADP/ATP carrier; uncoupling protein
• ISSN: 0066-4154; 1545-4509
• DOI: 10.1146/annurev-biochem-072820-020508

Members of the mitochondrial carrier family [solute carrier family 25 (SLC25)] transport nucleotides, amino acids, carboxylic acids, fatty acids, inorganic ions, and vitamins across the mitochondrial inner membrane. They are important for many cellular processes, such as oxidative phosphorylation of lipids and sugars, amino acid metabolism, macromolecular synthesis, ion homeostasis, cellular regulation, and differentiation. Here, we describe the functional elements of the transport mechanism of mitochondrial carriers, consisting of one central substrate-binding site and two gates with salt-bridge networks on either side of the carrier. Binding of the substrate during import causes three gate elements to rotate inward, forming the cytoplasmic network and closing access to the substrate-binding site from the intermembrane space. Simultaneously, three core elements rock outward, disrupting the matrix network and opening the substrate-binding site to the matrix side of the membrane. During export, substrate binding triggers conformational changes involving the same elements but operating in reverse.