LACTB is a mammalian active-site serine protein that has evolved from a bacterial penicillin-binding protein. Penicillin-binding proteins are involved in the metabolism of peptidoglycan, the major bacterial cell wall constituent, implying that LACTB has been endowed with novel biochemical properties during eukaryote evolution. Here we demonstrate that LACTB is localized in the mitochondrial intermembrane space, where it is polymerized into stable filaments with a length extending more than a hundred nanometers. We infer that LACTB, through polymerization, promotes intramitochondrial membrane organization and micro-compartmentalization. These findings have implications for our understanding of mitochondrial evolution and function. M itochondria descend from ancient Gram-negative bacteria that, through endosymbiosis, became permanent residents of eukaryotic cells (1-3). As a consequence, mitochondria and Gram-negative bacteria share several biochemical features, including DNA organization, core metabolism, and a doublemembrane architecture. In Gram-negative bacteria, but not in mitochondria, a mesh-like layer of peptidoglycan is deposited between the outer and inner membrane, offering protection against mechanical stress. Following endosymbiosis, the peptidoglycan layer lost its structural importance, and was subsequently eliminated from the early eukaryotic cell. Although eukaryotes lack peptidoglycan, proteins deriving from the penicillin-binding protein (PBP) family (4) are found in all major eukaryotic lineages, including vertebrates (5).The bacterial PBPs constitute a large family of serine proteases that is distinguished by 3 conserved amino acid motifs that contribute to the formation of the catalytic site. The -SXXKmotif contains the catalytic serine residue, which undergoes reversible acylation through substrate binding, whereas the -[SY]X[NT]-and the - [KH][ST]G-motifs contribute to substrate docking (4). PBPs catalyze the hydrolysis or transpeptidation of the terminal D-alanyl-D-alanine moiety in peptidoglycan stem peptides. The acceptor for the transpeptidation reaction is the -amino group of lysine or diaminopimelate in an adjacent stem peptide. Through these reactions, PBPs contribute to modulate the extent of peptidoglycan cross-linking during bacterial cell division and cell wall elongation (4).In contrast, the function of PBP homologues in eukaryotic organisms remains largely unexplored. Amino acid sequence analyses show that the 3 conserved amino acid motifs required for catalytic activity are conserved in all eukaryotic PBP homologues (5), suggesting that they can function as active-site serine enzymes. Within the metazoan division, nematodes harbor the largest number of PBP homologues (5), and in Caenorhabditis elegans the PBP homologue LACT-1 may be involved in pathogen recognition (6). LACTB is the only PBP homologue of mammals, and LACTB has been identified in all mammalian genomes sequenced to date (5,7,8). Recently, a causative link between LACTB and obesity was detected through gene coexp...

Background: Bacterial penicillin-binding proteins and β-lactamases (PBP-βLs) constitute a large family of serine proteases that perform essential functions in the synthesis and maintenance of peptidoglycan. Intriguingly, genes encoding PBP-βL homologs occur in many metazoan genomes including humans. The emerging role of LACTB, a mammalian mitochondrial PBP-βL homolog, in metabolic signaling prompted us to investigate the evolutionary history of metazoan PBP-βL proteins.

Ursolic acid (1), a pentacyclic triterpene acid, is one of the major components of certain traditional medicinal plants and possesses a wide range of biological effects, such as anti-inflammatory, antioxidative, and cytotoxic activities. Furthermore, 1, when present at 1.6-5 ng/mL concentrations in commercial herbal preparations used for patients with cardiac disorders, may also exert pro-cardiac activities. There are several indirect suggestions that the cardioprotective mechanism of ursolic acid could involve the mitochondria; however the mechanism of action is still not known. Therefore, the effects of 0.4-200 ng/mL ursolic acid (1) on the functions of isolated rat heart mitochondria oxidizing either pyruvate and malate, succinate, or palmitoyl-l-carnitine plus malate were investigated. It was found that 1 induced a statistically significant uncoupling of oxidative phosphorylation. A statistically significant decrease in H₂O₂ production in the mitochondria was observed after incubation with 5 ng/mL 1. This effect was comparable to the effectiveness of the classical uncoupler carbonyl cyanide 3-chlorophenylhydrazone. Since mild mitochondrial uncoupling has been proposed as one of the mechanisms of cardioprotection, the present results indicate that ursolic acid (1) has potential use as a cardioprotective compound.

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Anthocyanins are biologically active water-soluble plant pigments that are responsible for blue, purple, and red colors in various plant parts—especially in fruits and blooms. Anthocyanins have attracted attention as natural food colorants to be used in yogurts, juices, marmalades, and bakery products. Numerous studies have also indicated the beneficial health effects of anthocyanins and their metabolites on human or animal organisms, including free-radical scavenging and antioxidant activity. Thus, our aim was to review the current knowledge about anthocyanin occurrence in plants, their stability during processing, and also the bioavailability and protective effects related to the antioxidant activity of anthocyanins in human and animal brains, hearts, livers, and kidneys.

Ursolic and oleanolic acids are secondary plant metabolites that are known to be involved in the plant defence system against water loss and pathogens. Nowadays these triterpenoids are also regarded as potential pharmaceutical compounds and there is mounting experimental data that either purified compounds or triterpenoid-enriched plant extracts exert various beneficial effects, including anti-oxidative, anti-inflammatory and anticancer, on model systems of both human or animal origin. Some of those effects have been linked to the ability of ursolic and oleanolic acids to modulate intracellular antioxidant systems and also inflammation and cell death-related pathways. Therefore, our aim was to review current studies on the distribution of ursolic and oleanolic acids in plants, bioavailability and pharmacokinetic properties of these triterpenoids and their derivatives, and to discuss their neuroprotective effects in vitro and in vivo.

Methylglyoxal (MG) (pyruvaldehyde) is a reactive carbonyl compound produced in glycolysis. MG can form covalent adducts on proteins resulting in advanced glycation end products that may alter protein function. Here we report that MG covalently modifies the mitochondrial permeability transition pore (PTP), a high conductance channel involved in the signal transduction of cell death processes. Incubation of isolated mitochondria with MG for a short period of time (5 min), followed by removal of excess free MG, prevented both ganglioside GD3-and Ca 2؉ -induced PTP opening and the ensuing membrane depolarization, swelling, and cytochrome c release. Under these conditions MG did not significantly interfere with mitochondrial substrate transport, respiration, or oxidative phosphorylation. The suppression of permeability transition was reversible following extended incubation in MG-free medium. Of the 29 physiological carbonyl and dicarbonyl compounds tested only MG and its analogue glyoxal were able to specifically alter the behavior of the PTP. Using a set of arginine-containing peptides, we found that the major MG-derived arginine adduct formed, following a short time exposure to MG, was the 5-hydro-5-methylimidazol-4-one derivative. These findings demonstrate that MG rapidly modifies the PTP covalently and stabilizes the PTP in the closed conformation. This is probably due to the formation of an imidazolone adduct on an arginine residue involved in the control of PTP conformation (Linder, M. D., Morkunaite-Haimi, S., Kinnunen, P. J. K., Bernardi, P., and Eriksson, O. (2002) J. Biol. Chem. 277, 937-942). We deduce that the permeability transition constitutes a potentially important physiological target of MG.