bims-cytox1 2018-03-11 papers

Biochem Biophys Res Commun. 2018 Mar 01. pii: S0006-291X(18)30464-9. [Epub ahead of print]

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

Nidhi Kuksal, Danielle Gardiner, Dake Qi, Ryan J Mailloux.

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. Mice heterozygous for NDUFS4 (NDUFS4+/-) did not display any significant changes in overall body or organ weight when compared to wild-type (WT) littermates. There were no changes in superoxide (O2●-)/hydrogen peroxide (H2O2) release from cardiac or liver mitochondria isolated from NDUFS4 ± mice. Using selective ROS release inhibitors, we found that complex III is a major source of ROS in WT and NDUFS4 ± cardiac mitochondria respiring under state 4 conditions. Subjecting hearts from NDUFS4 ± mice to reperfusion injury revealed that the partial loss of complex I decreases contractile recovery and increases myocardial infarct size. These results correlated with a significant increase in O2●-/H2O2 release rates in mitochondria isolated from NDUFS4 ± hearts subjected to an IR challenge. Taken together, these results demonstrate that the partial absence of complex I sensitizes the myocardium towards IR injury and that the main source of ROS following reperfusion is complex III.

Keywords: Complex I; Heart; Ischemia-reperfusion; Mitochondria; NDUFS4; Reactive oxygen species

DOI: https://doi.org/10.1016/j.bbrc.2018.02.208

Mitochondrion. 2018 Feb 28. pii: S1567-7249(17)30331-8. [Epub ahead of print]

CPEO - Like mitochondrial myopathy associated with m.8340G>A mutation.

Mark A Tarnopolsky, Arun N E Sundaram, John Provias, Lauren Brady, Bekim Sadikovic.

Two patients with an m.8340G>A mitochondrial DNA variant have been reported with one patient showing ptosis, ophthalmoparesis and myopathy at 53% heteroplasmy and another with pigmentary retinopathy, cataracts and sensory neural deafness and slightly higher heteroplasmy (65%). Here we report that higher muscle mutant heteroplasmy (93%) for m.8340G>A is associated with ptosis, ophthalmoparesis and mitochondrial myopathy, thus confirming the initial phenotypic association and showing that heteroplasmy per se does not explain the phenotypic spectrum of disease associated with the m.8340G>A mutation.

DOI: https://doi.org/10.1016/j.mito.2018.02.008

Pediatr Clin North Am. 2018 Apr;pii: S0031-3955(17)30187-6. [Epub ahead of print]65(2): 375-388

Complex Phenotypes in Inborn Errors of Metabolism: Overlapping Presentations in Congenital Disorders of Glycosylation and Mitochondrial Disorders.

Thatjana Gardeitchik, Jeroen Wyckmans, Eva Morava.

Congenital disorders of glycosylation (CDG) and mitochondrial disorders have overlapping clinical features, including central nervous system, cardiac, gastrointestinal, hepatic, muscular, endocrine, and psychiatric disease. Specific abnormalities orienting the clinician toward the right diagnostic approach include abnormal fat distribution, coagulation abnormalities, together with anticoagulation abnormalities, hyperinsulinism, and congenital malformations in CDG. Diabetes, sensorineural deafness, and depression are very rare in CDG but common in mitochondrial disease. Chronic lactic acidosis is highly suggestive of mitochondrial dysfunction. Serum transferrin isoform analysis is specific for glycosylation abnormalities but not abnormal in all types of CDG.

Keywords: Cholestasis; Cutis laxa; Glycosylation; Hypoglycemia; Lactic acid; Mitochondrial disease; Stroke-like episodes; Transferrin isoelectric focusing (TIEF)

DOI: https://doi.org/10.1016/j.pcl.2017.11.012