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Tissue differentiation and proliferation throughout fetal development interconnect with changes in the oxidative phosphorylation system (OXPHOS) on the cellular level. Reevaluation of the expression data revealed a significant increase in COX4 and MTATP6 liver transcription levels after the 22nd gestational week (GW) which inspired us to characterize its functional impact. Specific activities of cytochrome c oxidase (COX), citrate synthase (CS), succinate-coenzyme Q reductase (SQR) and mtDNA determined by spectrophotometry and RT-PCR were studied in a set of 25 liver and 18 skeletal muscle samples at 13th to 29th GW. Additionally, liver hematopoiesis (LH) was surveyed by light microscopy. The mtDNA content positively correlated with the gestational age only in the liver. The activities of COX, CS and SQR in both liver and muscle isolated mitochondria significantly decreased after the 22nd GW in comparison with earlier GW. A continuous decline of LH, not correlating with the documented OXPHOS-specific activities, was observed from the 14th to the 24th GW indicating their exclusive reflection of liver tissue processes. Two apparently contradictory processes of increasing mtDNA transcription and decreasing OXPHOS-specific activities seem to be indispensable for rapid postnatal adaptation to high energy demands. The inadequate capacity of mitochondrial energy production may be an important factor in the mortality of children born before the critical developmental point of the 22nd GW. [ABSTRACT FROM AUTHOR]

Eukaryotic cytochrome c oxidase (CcO), the terminal component of the mitochondrial electron transport chain is a heterooligomeric complex that belongs to the superfamily of heme-copper containing terminal oxidases. The enzyme, composed of both mitochondrially and nuclear encoded subunits, is embedded in the inner mitochondrial membrane, where it catalyzes the transfer of electrons form reduced cytochrome c to dioxygen, coupling this reaction with vectorial proton pumping across the inner membrane. Due to the complexity of the enzyme, the biogenesis of CcO involves a multiplicity of steps, carried out by a number of highly specific gene products. These include mainly proteins that mediate the delivery and insertion of copper ions, synthesis and incorporation of heme moieties and membrane-insertion and topogenesis of constituent protein subunits. Isolated CcO deficiency represents one of the most frequently recognized causes of respiratory chain defects in humans, associated with severe, often fatal clinical phenotype. Here we review recent advancements in the understanding of this intricate process, with a focus on mammalian enzyme. [ABSTRACT FROM AUTHOR]

Freshly laid eggs from parent stock of Ross 308 at the age 31 weeks were used in the experiment. They were divided into five groups; fresh eggs (WP - without preincubation), preincubated once per 4 h (PS1 - one short preincubation), preincubated twice for 4 h (PS2 - two short preincubations), preincubated once per 8 h (PL1 - one long preincubation) and preincubated twice per 8 h (PL2 - tow long preincubation). Preincubated eggs were incubated after 5 and 10 days of storage for 4 or 8 h. In fresh eggs and after each treatment 60 eggs were examined for embryo development. After distinguish the egg status (fertilized or not), blastoderm was isolated and cleaned off the eggwhite and yolk, and then analyzed under the stereo microscope and staged according to Eyal-Giladi and Kochav (EGK, Roman numerals) procedure. However not all embryos were successfully isolated. The following numbers of embryos were successfully determined: WP - 23, PS1 - 25, PS2 - 10, PL1 - 20, PL2 - 8. Because of discrete nature of data with low number of variants, nonparametric Kruskal-Wallis ANOVA with subsequent pairwise comparisons was used for evaluation. Two statistically different groups were detected; the first one was created by WP (median X) and PS1 (median XI), the second one by PL1 (median XII - XIII), PS2 (median XIII) and PL2 (median XIII). It seems that second long term (8 h) preincubation does not significantly improve embryo development. Anyway this should be confirmed by staging higher number of embryos. [ABSTRACT FROM AUTHOR]

Background Mitochondrial myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes syndrome (MELAS) is a common mitochondrial disorder with varying multisystemic clinical manifestation. We present a comprehensive clinical picture of 50 Czech m.3243A> G carriers with emphasis on the sequence of symptoms in symptomatic patients. Results Symptoms developed in 33 patients (66%) and 17 carriers remained unaffected (34%). The age of onset varied from 1 month to 47 years of age, with juvenile presentation occurring in 53% of patients. Myopathy was the most common presenting symptom (18%), followed by CPEO/ptosis and hearing loss, with the latter also being the most common second symptom. Stroke-like episodes (SLE) occurred in fourteen patients, although never as a first symptom, and were frequently preceded by migraines (58%). Rhabdomyolysis developed in two patients. The second symptom appeared 5.0 ± 8.3 years (range 0–28 years) after the first, and the interval between the second and third symptom was 2.0 ± 6.0 years (range 0–21 years). Four of our patients remained monosymptomatic up to 12 years of follow-up. The sequence of symptoms according to their time of manifestation was migraines, myopathy, seizures, CPEO/ptosis, SLE, hearing loss, and diabetes mellitus. The average age at death was 32.4 ± 17.7 years (range 9–60 years) in the juvenile form and 44.0 ± 12.7 years (range 35–53 years) in the adult form. Some patients with SLE harboured very low heteroplasmy levels in various tissues. No threshold for any organ dysfunction could be determined based on these levels. Conclusions Sufficient knowledge of the timeline of the natural course of MELAS syndrome may improve the prediction and management of symptoms in patients with this mitochondrial disease. [ABSTRACT FROM AUTHOR]