Biomaterial Database

Mechanism of mitochondrial import of adenylate kinase isozymes. 1998

M Nobumoto, and M Yamada, and S Song, and S Inouye, and A Nakazawa

Center for Gene Research, Yamaguchi University, Ube.

Adenylate kinase (AK) is a ubiquitous enzyme that contributes to the homeostasis of the cellular adenine nucleotide composition. Three isozymes, AK1, AK2, and AK3, have so far been characterized in vertebrates. They are located in different tissues, while their primary and tertiary structures are similar. Among them, AK2 and AK3 are located in mitochondria, but unlike most mitochondrial proteins, both proteins lack a cleavable presequence. In this study, we first confirmed that AK2 is distributed in liver cells in both the cytosol and the intermembrane space of mitochondria, while AK3 is localized exclusively in the mitochondrial matrix. Next, we analyzed the process of import of AK2 and AK3 by incubating isolated rat mitochondria with proteins that were synthesized in a reticulocyte lysate translation system. The results indicated that both AK2 (an intermembrane-space-targeting protein) and AK3 (a matrix-targeting protein) require an inner membrane electrochemical potential for their import. This finding for AK2 is in contrast with those of other noncleavable intermembrane-space-targeting proteins such as cytochrome c and cytochrome c heme lyase, which do not require the membrane potential for their import. In the transport process, AK2 and AK3 competed with the adrenodoxin precursor, which is imported into the matrix through a mechanism common to other mitochondrial matrix proteins. Thus, AK2 and AK3 were thought to be translocated into mitochondria through the same pathway as that for most mitochondrial protein precursors. Neither AK2, that was previously synthesized in reticulocyte lysates, nor AK2, that was purified from an Escherichia coli overexpression system, was imported into mitochondria in a post-translational import manner. In contrast, AK3 was imported into mitochondria after completion of protein synthesis. Thus, the import of AK2 is likely to be co-translational, and the co-translational import mechanism might contribute to the bi-topological distribution of AK2 in both the cytosol and mitochondria.

UI	MeSH Term	Description	Entries
D007202	Indicators and Reagents	Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)	Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D007425	Intracellular Membranes	Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.	Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008930	Mitochondria, Liver	Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)	Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D011498	Protein Precursors		Precursors, Protein
D011500	Protein Synthesis Inhibitors	Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.	Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
D004072	Digitonin	A glycoside obtained from Digitalis purpurea; the aglycone is digitogenin which is bound to five sugars. Digitonin solubilizes lipids, especially in membranes and is used as a tool in cellular biochemistry, and reagent for precipitating cholesterol. It has no cardiac effects.	Digitin
D000263	Adenylate Kinase	An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.	Myokinase,AMP Kinase,ATP-AMP Phosphotransferase,ATP-AMP Transphosphorylase,Adenylokinase,ATP AMP Phosphotransferase,ATP AMP Transphosphorylase,Kinase, AMP,Kinase, Adenylate,Phosphotransferase, ATP-AMP,Transphosphorylase, ATP-AMP