Identification of the Mitochondrial MSRB2 as a Binding Partner of LG72

Abstract

Genetic studies have linked the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in the etiology of schizophrenia and other psychiatric disorders.However, the function of the protein encoded by this locus, LG72, is currently controversially discussed. Some studies have suggested that LG72 binds to and regulates the activity of the peroxisomal enzyme D-amino-acid-oxidase, while others proposed an alternative role of this protein due to its mitochondrial location in vitro.Studies with transgenic mice expressing LG72 further suggested that high levels ofLG72 lead to an impairment of mitochondrial functions with a concomitant increase in reactive oxygen species (ROS) production. In the present study we now performed extensive interaction analyses and identified the mitochondrial methionine-Rsulfoxide reductase B2 (MSRB2) as a specific interaction partner of LG72. MSRB2 belongs to the MSR protein family and functions in mitochondrial oxidative stress defense. Based on our results we propose that LG72 is involved in the regulation of mitochondrial oxidative stress.

Expression of D-Amino Acid Oxidase (DAO/DAAO) and D-Amino Acid Oxidase Activator (DAOA/G72) during Development and Aging in the Human Post-mortem Brain

“…This is because DAOA is reported to both increase (Chumakov et al, 2002; Chang et al, 2014) and decrease (Sacchi et al, 2008, 2011) the activity of DAO. DAOA is localized in mitochondria and reported to modulate its function (Kvajo et al, 2008; Sacchi et al, 2011; Otte et al, 2014). Thus, the exact function of DAOA is not yet completely understood.…”

Synaptic and cellular changes induced by the schizophrenia susceptibility gene G72 are rescued by N-acetylcysteine treatment

“… 21 Recently, the mitochondrial enzyme methionine-R-sulfoxide reductase B2 has been identified as a binding partner of LG72, suggesting that LG72 can influence oxidative stress regulation. 20 Subcellular localization and the ability of LG72 to bind flavin-containing proteins also suggest a connection between LG72 and complex I of the mitochondrial respiratory chain. 23 Complex I is often affected in schizophrenia and bipolar disorder.…”

“…It has been demonstrated to bind D-amino acid oxidase (DAO), the main degrading enzyme of NMDAR co-agonist D-serine, 17 resulting in either enhancement or depression of its enzymatic function. 14 , 18 , 19 Furthermore, LG72 has been shown to be located in mitochondria, influencing oxidative stress regulation 20 and affecting mitochondrial morphology and dendritic arborization. 21 …”

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

“…We then investigated whether other mitochondrial proteases or repair proteins may compensate for Lon depletion. We focused on two proteins, namely ClpP, the second other protease localized in the mitochondrial matrix, and MsrB2 involved in oxidized protein repair, [4] [32].…”