Developmental changes in mitochondria during the transition into lactation in the mouse mammary gland

Abstract

Mitochondrial biogenesis in the parenchymal cell of the mouse mammary gland appears to occur in two distinct phases: replication during cell proliferation, and maturation during cell differentiation. This study of the mitochondrial maturation phase in the mouse gland demonstrates a significant increase in organelle density on isopycnic sucrose gradient centrifugation during the transition from late pregnancy to day 8 of lactation. Differential fragility to high sucrose concentrations or changes in mitochondrial lipid composition do not satisfactorily explain the density increases. When organelle densities were assessed by centrifugation under iso-osmotic conditions with Ficoll gradients in 0.25 M sucrose, the mitochondria from pregnant glands were observed to be more dense than those from lactating glands. The two mitochondrial populations were also found to differ in their response to changes in sucrose concentration in the Ficoll gradients. When sucrose concentration was increased, the density of both pregnant and lactating gland mitochondria increased nonlinearly, the increase being greater with the lactating gland organelles. By use of mathematical models, the differing response was interpreted as a change in the density and osmotic activity of the mitochondrial internal compartment (inner membrane plus matrix space). We have proposed that the changes reflect a large expansion of the inner mitochondrial membrane and perhaps the matrix material during the transition into lactation in the differentiating parenchymal cell.

PIP: Developmental changes in mitochondria during pregnancy and the transition into lactation in the parenchymal cell of the mouse mammary gland were studied. There were 2 apparent distinct phases in mitochondrial biogenesis: replication during cell proliferation and maturation during cell differentiation. Isopycnic sucrose gradient centrifugation during the transition from late pregnancy to Day 8 of lactation revealed a marked increase in organelle density. This increase in organelle density could not be explained by differential fragility to high sucrose concentrations or changes in mitochondrial lipid composition. Mitochondria from pregnant glands were more dense than those from lactating glands as determined by centrifugation under iso-osmotic conditions with Ficoll gradients in .25 M sucrose. These mitochondrial populations also differed in their response to changes in the concentration of sucrose in the Ficoll gradients. The density of both pregnant and lactating gland mitochondria increased nonlinearly when the sucrose concentration was increased, with the increase in density being greater in the latter. The difference in response was mathematically interpreted to reflect a change in the density and osmotic activity of the mitochondrial internal compartment (inner membrane plus matrix space). It is proposed that the developmental changes observed reflect a large expansion of the inner mitochondrial membrane and possibly the matrix material during the transition into lactation in the differentiating parenchymal cell.