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Title: Intramitochondrial protein synthesis is regulated by matrix adenine nucleotide content and requires calcium. Author: Joyal JL, Hagen T, Aprille JR. Journal: Arch Biochem Biophys; 1995 May 10; 319(1):322-30. PubMed ID: 7539604. Abstract: The hypothesis that fluctuations in matrix adenine nucleotide content (ATP + ADP + AMP) may regulate intramitochondrial protein synthesis was investigated in newborn and adult rat liver mitochondria. Protein synthesis in mitochondria from 0-h-old newborns, which contain 3.4 +/- 0.3 nmol adenine nucleotide/mg protein, was > 90% lower than protein synthesis in mitochondria from 4-h-old newborns, which contain 9.1 +/- 0.2 nmol adenine nucleotide/mg protein. If 0-h newborn mitochondria were preincubated to accumulate adenine nucleotides to 16.8 nmol/mg protein in vitro, the protein synthesis rate increased 25-fold compared to control. Adult rat liver mitochondria normally contain 12-14 nmol adenine nucleotide/mg protein and exhibit a brisk rate of protein synthesis. Following a preincubation to deplete adenine nucleotides in vitro down to 3 nmol/mg protein, protein synthesis in adult liver mitochondria was nearly abolished. Conversely, when adult mitochondria were preincubated to superload adenine nucleotides (to 29 nmol/mg protein), the rate of protein synthesis was doubled. Protein synthesis was also inhibited when the matrix ATP/ADP ratio was lowered by adding FCCP or by omitting phosphate. In adult mitochondria, protein synthesis was inhibited by 0.5 mM EGTA and was increased in proportion to buffered free calcium between 0 and 20 microM. The rate of intramitochondrial RNA synthesis was not inhibited by EGTA nor affected by variations in matrix adenine nucleotide content. The results show that intramitochondrial translation requires matrix calcium and is regulated by changes in the matrix adenine nucleotide content that affect the matrix ATP concentration. The matrix adenine nucleotide content is controlled by the ATP-Mg/Pi carrier. In newborns, the matrix adenine nucleotide content increases 3-fold within 2-4 h after birth, stimulating mitochondrial translation 10-fold and probably contributing to the onset of postnatal mitochondrial biogenesis and adaptation to aerobic metabolism.[Abstract] [Full Text] [Related] [New Search]