Deletion of the Glutaredoxin-2 Gene Protects Mice from Diet-Induced Weight Gain, Which Correlates with Increased Mitochondrial Respiration and Proton Leaks in Skeletal Muscle.

The aim of this study was to determine whether deleting the gene encoding glutaredoxin-2 (GRX2) could protect mice from diet-induced weight gain. Subjecting wild-type littermates to a high fat diet (HFD) induced a significant increase in overall body mass, white adipose tissue hypertrophy, lipid droplet accumulation in hepatocytes, and higher circulating insulin and triglyceride levels. In contrast, GRX2 heterozygotes (GRX2) fed an HFD had a body mass, white adipose tissue weight, and hepatic and circulating lipid and insulin levels similar to littermates fed a control diet.

Estimation of the hydrogen peroxide producing capacities of liver and cardiac mitochondria isolated from C57BL/6N and C57BL/6J mice.

Here, we examined the hydrogen peroxide (HO) producing capacities of pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (KGDH), proline dehydrogenase (PRODH), glycerol-3-phosphate dehydrogenase (G3PDH), succinate dehydrogenase (SDH; complex II), and branched-chain keto acid dehydrogenase (BCKDH), in cardiac and liver mitochondria isolated from C57BL/6N (6N) and C57BL/6J (6J) mice. Various inhibitor combinations were used to suppress ROS production by complexes I, II, and III and estimate the native rates of HO production for these enzymes. Overall, liver mitochondria from 6N mice produced ∼2-fold more ROS than samples enriched from 6J mice.

Partial loss of complex I due to NDUFS4 deficiency augments myocardial reperfusion damage by increasing mitochondrial superoxide/hydrogen peroxide production.

Recent work has found that complex I is the sole source of reactive oxygen species (ROS) during myocardial ischemia-reperfusion (IR) injury. However, it has also been reported that heart mitochondria can also generate ROS from other sources in the respiratory chain and Krebs cycle. This study examined the impact of partial complex I deficiency due to selective loss of the Ndufs4 gene on IR injury to heart tissue.

Characterization of the impact of glutaredoxin-2 (GRX2) deficiency on superoxide/hydrogen peroxide release from cardiac and liver mitochondria.

Mitochondria are critical sources of hydrogen peroxide (HO), an important secondary messenger in mammalian cells. Recent work has shown that O/HO emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O/HO release rates from cardiac and liver mitochondria isolated from mice deficient for glutaredoxin-2 (GRX2), a matrix-associated thiol oxidoreductase that facilitates the S-glutathionylation and deglutathionylation of proteins.

Progress in understanding the molecular oxygen paradox - function of mitochondrial reactive oxygen species in cell signaling.

The molecular oxygen (O2) paradox was coined to describe its essential nature and toxicity. The latter characteristic of O2 is associated with the formation of reactive oxygen species (ROS), which can damage structures vital for cellular function. Mammals are equipped with antioxidant systems to fend off the potentially damaging effects of ROS.

Examination of the superoxide/hydrogen peroxide forming and quenching potential of mouse liver mitochondria.

Pyruvate dehydrogenase (PDHC) and α-ketoglutarate dehydrogenase complex (KGDHC) are important sources of reactive oxygen species (ROS). In addition, it has been found that mitochondria can also serve as sinks for cellular hydrogen peroxide (HO). However, the ROS forming and quenching capacity of liver mitochondria has never been thoroughly examined.