Proteomic profiling of Sengers patient fibroblasts and AGK knockout models identifies remodeling the mitochondrial proteome, including one-carbon metabolism enzymes, inner membrane serine transporters, sideroflexins, Complex I subunits assembly factors.

RATIONALE Pyridine nucleotides regulate the cardiac Na(+) current (I(Na)) through generation of reactive oxygen species (ROS). OBJECTIVE We investigated the source of ROS induced by elevated NADH. METHODS AND RESULTS In human embryonic kidney (HEK) cells stably expressing the cardiac Na(+) channel, the decrease of I(Na) (52±9%; P<0.01) induced by cytosolic NADH application (100 μmol/L) was ...

Complex I (NADH:ubiquinone oxidoreductase) is central to cellular NAD(+) recycling and accounts for approximately 40% of mitochondrial ATP production. To understand how complex I function impacts respiration and plant development, we isolated Arabidopsis (Arabidopsis thaliana) lines that lack complex I activity due to the absence of the catalytic subunit NDUFV1 (for NADH:ubiquinone oxidoreducta...

Mitochondrial reactive oxygen species (ROS) have emerged as an important mechanism of disease and redox signaling in the cardiovascular system. Under basal or pathological conditions, electron leakage for ROS production is primarily mediated by the electron transport chain and the proton motive force consisting of a membrane potential (ΔΨ) and a proton gradient (ΔpH). Several factors controllin...

The mitochondrial NADH dehydrogenase complex (complex I) is of particular importance for the respiratory chain in mitochondria. It is the major electron entry site for the mitochondrial electron transport chain (mETC) and therefore of great significance for mitochondrial ATP generation. We recently described an Arabidopsis thaliana double-mutant lacking the genes encoding the carbonic anhydrase...

Mitochondrial transformation of Chlamydomonas reinhardtii has been optimized by using a particle-gun device and cloned mitochondrial DNA or PCR fragments. A respiratory-deficient strain lacking a 1.2-kb mitochondrial DNA region including the left telomere and part of the cob gene could be rescued as well as a double-frameshift mutant in the mitochondrial cox1 and nd1 genes. High transformation ...

Many Caenorhabditis elegans mutants with dysfunctional mitochondrial electron transport chain are surprisingly long lived. Both short-lived (gas-1(fc21)) and long-lived (nuo-6(qm200)) mutants of mitochondrial complex I have been identified. However, it is not clear what are the pathways determining the difference in longevity. We show that even in a short-lived gas-1(fc21) mutant, many longevit...

Oxidative stress and mitochondrial dysfunction signify important biochemical events associated with the loss of dopaminergic neurons in Parkinson’s disease (PD). Studies using in vitro and in vivo PD models or tissues from diseased patients have demonstrated a selective inhibition of mitochondrial NADH dehydrogenase (Complex I of the OXPHOS electron transport chain) that affects normal mitochon...