naa a22 4500 510775861 CHVBK 20180411083230.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s12975-013-0278-x doi (NATIONALLICENCE)springer-10.1007/s12975-013-0278-x Mitochondrial Dysfunction and NAD+ Metabolism Alterations in the Pathophysiology of Acute Brain Injury [Elektronische Daten] [Katrina Owens, Ji Park, Rosemary Schuh, Tibor Kristian] Mitochondrial dysfunction is commonly believed to be one of the major players in mechanisms of brain injury. For several decades, pathologic mitochondrial calcium overload and associated opening of the mitochondrial permeability transition (MPT) pore were considered a detrimental factor causing mitochondrial damage and bioenergetics failure. Mitochondrial and cellular bioenergetic metabolism depends on the enzymatic reactions that require NAD+ or its reduced form NADH as cofactors. Recently, it was shown that NAD+ also has an important function as a substrate for several NAD+ glycohydrolases whose overactivation can contribute to cell death mechanisms. Furthermore, downstream metabolites of NAD+ catabolism can also adversely affect cell viability. In contrast to the negative effects of NAD+-catabolizing enzymes, enzymes that constitute the NAD+ biosynthesis pathway possess neuroprotective properties. In the first part of this review, we discuss the role of MPT in acute brain injury and its role in mitochondrial NAD+ metabolism. Next, we focus on individual NAD+ glycohydrolases, both cytosolic and mitochondrial, and their role in NAD+ catabolism and brain damage. Finally, we discuss the potential effects of downstream products of NAD+ degradation and associated enzymes as well as the role of NAD+ resynthesis enzymes as potential therapeutic targets. Springer Science+Business Media New York, 2013 Mitochondria nationallicence Nicotinamide adenine dinucleotide nationallicence Ischemia nationallicence Brain nationallicence Owens Katrina Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut Park Ji Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut Schuh Rosemary Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut Kristian Tibor Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 618-634 1868-4483 4:6<618 2013 4 12975 https://doi.org/10.1007/s12975-013-0278-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-013-0278-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Owens Katrina Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Park Ji Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Schuh Rosemary Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Kristian Tibor Veterans Affairs Maryland Health Care System, 10 North Greene Street, 21201, Baltimore, MD, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 618-634 1868-4483 4:6<618 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer