Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replace...

Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P < 0.01) i.v. infused with insulin (1.5 milliunits/kg of fat-free mass per...

ATP in neurons is commonly believed to be synthesized mostly by mitochondria via oxidative phosphorylation. Neuronal mitochondria have been studied primarily in culture, i.e., in neurons isolated either from embryos or from neonatal pups. Although it is generally assumed that both embryonic and postnatal cultured neurons derive their ATP from mitochondrial oxidative phosphorylation, this has ne...

F1Fo-ATP synthase (ATP synthase) is a central membrane protein that synthetizes most of the ATP in cell through rotational movement driven by proton gradient across hosting membrane. In mitochondria, synthases can form dimers specific interactions between some subunits protein. The dimeric provides with spontaneous curvature sustain their arrangement at rim high-curvature edges mitochondrial (c...

Introduction. It has been suggested that an impairment in skeletal muscle mitochondrial function plays a causative role in the development of insulin resistance and type 2 diabetes [1]. This hypothesis is predominantly based on in vitro measurements of for example gene expression and in vivo measurements of basal ATP synthesis flux with P MR saturation transfer (ST) experiments. However, the in...

Mutations in human mitochondrial DNA are a well recognized cause of disease. A mutation at nucleotide position 8993 of human mitochondrial DNA, located within the gene for ATP synthase subunit 6, is associated with the neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome. To enable analysis of this mutation in control nuclear backgrounds, two different cell lines were ...

Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes bec...

Mitochondria sustain cellular life through energy production but also mediate programmed cell death. ATP production is mainly via cellular respiration, which is driven by the voltage gradient (ΔΨ m ) across the inner mitochondrial membrane that drives proton flux through the F 0 F 1 –ATP synthase. Extremely low resting inner mitochondrial membrane permeability is critical to maintain high ΔΨ m ...

Mitochondrial dysfunction (depolarization and structural collapse), cytosolic ATP depletion, and neuritic beading are early hallmarks of neuronal toxicity induced in a variety of pathological conditions. We show that, following global exposure to glutamate, mitochondrial changes are spatially and temporally coincident with dendritic bead formation. During oxygen-glucose deprivation, mitochondri...

Mitochondrial metabolism is a critical component in the functioning and maintenance of cellular organs. The stoichiometry of biochemical reaction networks imposes constraints on mitochondrial function. A modeling framework, flux-balance analysis (FBA), was used to characterize the optimal flux distributions for maximal ATP production in the mitochondrion. The model predicted the expected ATP yi...