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SIRT3, the primary mitochondrial deacetylase, regulates the functions of mitochondrial proteins including metabolic enzymes and respiratory chain components. Although SIRT3's functions in peripheral tissues are well established, the significance of its downregulation in neurodegenerative diseases is beginning to emerge. SIRT3 plays a key role in brain energy metabolism and provides substrate flexibility to neurons. It also facilitates metabolic coupling between fuel substrate-producing tissues and fuel-consuming tissues. SIRT3 mediates the health benefits of lifestyle-based modifications such as calorie restriction and exercise. SIRT3 deficiency is associated with metabolic syndrome (MetS), a precondition for diseases including obesity, diabetes, and cardiovascular disease. The pure form of Alzheimer's disease (AD) is rare, and it has been reported to coexist with these diseases in aging populations. SIRT3 downregulation leads to mitochondrial dysfunction, neuroinflammation, and inflammation, potentially triggering factors of AD pathogenesis. Recent studies have also suggested that SIRT3 may act through multiple pathways to reduce plaque formation in the AD brain. In this review, we give an overview of SIRT3's roles in brain physiology and pathology and discuss several activators of SIRT3 that can be considered potential therapeutic agents for the treatment of dementia. [ABSTRACT FROM AUTHOR]

The production of reactive nitrogen species (RNS) by the innate immune system is part of the host's defense against invading pathogenic bacteria. In this review, we summarize recent studies on the molecular basis of the effects of nitric oxide and peroxynitrite on microbial respiration and energy conservation. We discuss possible molecular mechanisms underlying RNS resistance in bacteria mediated by unique respiratory oxygen reductases, the mycobacterial bcc-aa3 supercomplex, and bd-type cytochromes. A complete picture of the impact of RNS on microbial bioenergetics is not yet available. However, this research area is developing very rapidly, and the knowledge gained should help us develop new methods of treating infectious diseases. [ABSTRACT FROM AUTHOR]

The world's seafood supply and trade have increased in the last decades, as well as the potential for marketed species substitution. Currently, seafood safety and authenticity assessment have become central issues, directly related with the identification of improper labeling of processed foods. To detect and prevent mislabeling issues, species identification using DNA barcodes has been widely used as effective molecular markers. Therefore, this review intends to present the current status on the application of DNA barcodes to seafood species authentication. In this regard, the barcode regions, reference databases and related methodologies are described, while applications are listed and summarized. Cytochrome c oxidase subunit I (COI) gene has been the preferential targeted DNA region in animal species identification, including fish and shellfish, though other mitochondrial (cytb, 12S rRNA, 16S rRNA) and nuclear genes have been used. DNA barcoding relying on Sanger's sequencing has been the most used approach for seafood authentication. Nevertheless, in recent years, noteworthy progresses have been advanced toward DNA barcoding strategies, involving next generation sequencing. Methods relying on real-time PCR using species-specific primers and probes or followed by high resolution melting analysis combined with DNA barcodes represent alternative and promising approaches for simple, cost-effective and high-throughput species discrimination in processed seafood. Still, polymerase chain reaction with restriction fragment length polymorphism detection, targeting DNA barcodes, continues to be a well-established and broadly accepted method in seafood authentication. [ABSTRACT FROM AUTHOR]

Aerobic respiration is a key energy-producing pathway in many prokaryotes and virtually all eukaryotes. The final step of aerobic respiration is most commonly catalyzed by heme-copper oxidases embedded in the cytoplasmic or mitochondrial membrane. The majority of these terminal oxidases contain a prenylated heme (typically heme a or occasionally heme o) in the active site. In addition, many heme-copper oxidases, including mitochondrial cytochrome c oxidases, possess a second heme a cofactor. Despite the critical role of heme a in the electron transport chain, the details of the mechanism by which heme b, the prototypical cellular heme, is converted to heme o and then to heme a remain poorly understood. Recent structural investigations, however, have helped clarify some elements of heme a biosynthesis. In this review, we discuss the insight gained from these advances. In particular, we present a new structural model of heme o synthase (HOS) based on distance restraints from inferred coevolutionary relationships and refined by molecular dynamics simulations that are in good agreement with the experimentally determined structures of HOS homologs. We also analyze the two structures of heme a synthase (HAS) that have recently been solved by other groups. For both HOS and HAS, we discuss the proposed catalytic mechanisms and highlight how new insights into the heme-binding site locations shed light on previously obtained biochemical data. Finally, we explore the implications of the new structural data in the broader context of heme trafficking in the heme a biosynthetic pathway and heme-copper oxidase assembly. [ABSTRACT FROM AUTHOR]

Peroxisomes hardly make an appearance in the book, apart from the fascinating history in which they inspired the search for the supposed (but non-existent) endosymbiotic precursor of the peroxisomes in "primitive eukaryotes", leading to the stunning discovery of hydrogenosomes, the rare incarnations of mitochondria able to synthesize H SB 2 sb . After stating that the "anaerobic eukaryotes" used to be the odd ones out, we find this: "In the modern context of late oxygenation in atmospheric evolution, it is now the strictly O SB 2 sb -dependent mitochondria that do not fit into the bigger picture, because they were only useful for the last third of eukaryotic evolution, placing the first two thirds of eukaryotic history into the era of anaerobes." The evolution of eukaryotic cells from the perspective of peroxisomes: Phylogenetic analyses of peroxisomal beta-oxidation enzymes support mitochondria-first models of eukaryotic cell evolution. Ever since doing my own oxygen consumption experiments with rat liver mitochondria, I have been impressed by the very low K SB m sb (high affinity) of cytochrome c oxidase for O SB 2 sb . [Extracted from the article]

The reversible interconversion of molecular hydrogen and protons is one of the most ancient microbial metabolic reactions and catalyzed by hydrogenases. A widespread yet largely enigmatic group comprises multisubunit [NiFe] hydrogenases, that directly couple H2 metabolism to the electrochemical ion gradient across the membranes of bacteria and of archaea. These complexes are collectively referred to as energy-converting hydrogenases (Ech), as they reversibly transform redox energy into physicochemical energy. Redox energy is typically provided by a low potential electron donor such as reduced ferredoxin to fuel H2 evolution and the establishment of a transmembrane electrochemical ion gradient ( Δ μ ~ ion ). The Δ μ ~ ion is then utilized by an ATP synthase for energy conservation by generating ATP. This review describes the modular structure/function of Ech complexes, focuses on insights into the energy-converting mechanisms, describes the evolutionary context and delves into the implications of relying on an Ech complex as respiratory enzyme for microbial metabolism. [ABSTRACT FROM AUTHOR]