ATP synthase or complex V (cV) of the oxidative phosphorylation system is responsible for the production of ATP, dissipating the electrochemical gradient generated by the mitochondrial respiratory ...chain. In addition to maternally transmitted cV dysfunction caused by mutations in mtDNA genes (MT-ATP6 or MT-ATP8), encoding cV subunits, recessive mutations in the nuclear TMEM70 are the most frequent cause of ATP synthase deficiency.
We report on a cohort of ten Italian patients presenting with neonatal lactic acidosis, respiratory distress, hypotonia, cardiomyopathy and psychomotor delay and harbouring mutations in TMEM70, including the common splice mutation and four novel variants. TMEM70 protein was virtually absent in all tested TMEM70 patients’ specimens.
The exact function of TMEM70 is not known, but it is considered to impact on cV assembly since TMEM70 mutations have been associated with isolated cV activity reduction. We detected a clear cV biochemical defect in TMEM70 patients’ fibroblasts, whereas the assay was not reliable in frozen muscle. Nevertheless, the evaluation of the amount of holocomplexes in patients with TMEM70 mutations showed a nearly absent cV in muscles and a strong decrease of cV with accumulation of sub-assembly species in fibroblasts. In our cohort we found not only cV deficiencies but also impairment of other OXPHOS complexes. By ultrastructural analysis of muscle tissue from one patient with isolated cV deficiency, we found a severely impaired mitochondrial morphology with loss of the cristae. These findings indicate that cV impairment could indirectly alter other respiratory chain complex activities by disrupting the mitochondrial cristae structure.
Various reports have documented the difficulty in assessing neonatal response to painful stimuli. The aim of our study was to evaluate previously described scales for assessing pain in a group of 18 ...healthy term newborns selected according to Prechtl's optimality criteria and subjected to a routine metabolic screening blood test performed on the 5th day of life. Both a modified CHEOPS scale and Grunau-Craig Scale, to assess pain behavior response before, during and after a painful stimulus, revealed definite modifications in scores. Response to pain was also evaluated by measuring variations in decreases in transcutaneous oxygen pressure in all newborns during application of the stimulus and in returns to baseline or higher values upon removal of the stimulus. Our study confirms that healthy term newborns feel pain when subjected to limited painful stimuli such as the routine blood test and suggests useful and easy methodological tools to evaluate pain in the newborn.
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