Accuracy and precision of quantitative 31P-MRS measurements of human skeletal muscle mitochondrial function

Although theoretically sound, the accuracy and precision of 31P-magnetic resonance spectroscopy (31P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control [linear, kinetic, and multipoint adenosine diphosphate (ADP) and phosphorylation potential], this study sought to determine the accuracy and precision of 31P-MRS assessments of peak mitochondrial adenosine-triphosphate (ATP) synthesis rate utilizing directly measured peak respiration (State 3) in permeabilized skeletal muscle fibers. In 23 subjects of different fitness levels, 31P-MRS during a 24-s maximal isometric knee extension and high-resolution respirometry in muscle fibers from the vastus lateralis was performed. Although significantly correlated with State 3 respiration ( r = 0.72), both the linear (45 ± 13 mM/min) and phosphorylation potential (47 ± 16 mM/min) models grossly overestimated the calculated in vitro peak ATP synthesis rate ( P < 0.05). Of the ADP models, the kinetic model was well correlated with State 3 respiration ( r = 0.72, P < 0.05), but moderately overestimated ATP synthesis rate ( P < 0.05), while the multipoint model, although being somewhat less well correlated with State 3 respiration ( r = 0.55, P < 0.05), most accurately reflected peak ATP synthesis rate. Of note, the PCr recovery time constant (τ), a qualitative index of mitochondrial capacity, exhibited the strongest correlation with State 3 respiration ( r = 0.80, P < 0.05). Therefore, this study reveals that each of the 31P-MRS data analyses, including PCr τ, exhibit precision in terms of mitochondrial capacity. As only the multipoint ADP model did not overstimate the peak skeletal muscle mitochondrial ATP synthesis, the multipoint ADP model is the only quantitative approach to exhibit both accuracy and precision.

Zika virus phosphoproteome through the computational looking-glass and what we found there?

Zika virus (ZIKV), a mosquito borne disease, has been linked to congenital anomalies in humans. Recent outbreaks of ZIKV have caused the scientific community to focus on this previously neglected pathogen. Information regarding phosphorylation potential of ZIKV proteins has yet to be elucidated. Deciphering phosphorylation potential of viral proteins is important because it assists in viral replication and its association with host receptors. Here, we present a vignette of the phosphorylation potential of ZIKV proteins using computational approach.

Zika virus phosphoproteome through the computational looking-glass and what we found there?

Zika virus (ZIKV), a mosquito borne disease, has been linked to congenital anomalies in humans. Recent outbreaks of ZIKV have caused the scientific community to focus on this previously neglected pathogen. Information regarding phosphorylation potential of ZIKV proteins has yet to be elucidated. Deciphering phosphorylation potential of viral proteins is important because it assists in viral replication and its association with host receptors. Here, we present a vignette of the phosphorylation potential of ZIKV proteins using computational approach.

Zika virus phosphoproteome through the computational looking-glass and what we found there?

Computational phospho-mining and related post translational modification analyses using in silico methods is debateable. For some wet lab scientists, it is similar to the twilight zone, where nothing might be quite what it seems. We certainly agree that the wet lab is critical for validation but computational assays rapidly generate preliminary data for assessment and aid wet lab. Zika virus is wrecking a havoc and it is the need of the hour to rapidly assess various phenomenon associated with its pathogenicity and disseminate it to the scientific community for assessment. Phosphorylation assists in viral replication and its association with host receptors. Here, we present a vignette of the phosphorylation potential of Zika virus proteins.