Microarray and qPCR Analysis of Mitochondrial Metabolism Activation during Prenatal and Early Postnatal Development in Rats and Humans with Emphasis on CoQ10 Biosynthesis

Simple Summary We lack studies investigating mitochondrial metabolism in the prenatal and early postnatal period in humans, but parallel experiments conducted in a mammalian system are informative about the human condition. Our aim was to study the perinatal metabolic switch in rats-an extremely complex process, associated with tissue proliferation and differentiation together with a rapid oxidative stress response (using techniques including microarrays, qPCR, spectrophotometry and high-performance liquid chromatography). Out of 1546 mitochondrial genes, 1119 and 827 genes significantly changed expression in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q and mitochondrial metabolism-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content and mitochondrial metabolism significantly increases after birth, possibly regulated by COQ8A kinase. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and preparation of the foetus for the transition to extra-uterine conditions, or as preliminary data for further studies of the complex mitochondrial metabolism regulation and diagnostics of mitochondrial disorders. At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI's Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.

Automated summary

Research findings suggest significant changes in over 1000 mitochondrial genes in both rat liver and skeletal muscle, with the most pronounced shift occurring at least two days before birth in rat liver. Evaluation of Coenzyme Q in both rat and human tissues shows a significant increase in total CoQ content and mitochondrial metabolism postnatally, potentially regulated by COQ8A kinase.