Mortimore G E, Hutson N J, Surmacz C A
Proc Natl Acad Sci U S A. 1983 Apr;80(8):2179-83. doi: 10.1073/pnas.80.8.2179.
Cytoplasmic protein in hepatocytes is sequestered and degraded by two general classes of lysosomes, overt autophagic vacuoles (macroautophagy) and dense bodies (microautophagy). Volumes of the apparent space in each class that contain the internalized protein, together with estimates of cytoplasmic protein concentration, were used as a basis for predicting rates of protein degradation by the lysosomal system in livers of fed, 48-hr starved, and starved-refed mice. Assuming that the turnover of all sequestered protein is equal to that previously determined in overt autophagic vacuoles (0.087 min-1), we obtained close agreement between predicted and observed rates in the three conditions studied. The two autophagic components, though, exhibited different patterns of regulation. Microautophagy followed a downward course through starvation and into refeeding, a trend that explained fully the fall in absolute rates of protein degradation during starvation. By contrast, macroautophagy remained constant throughout starvation but was virtually abolished with refeeding. Whereas regulation of the latter can be explained largely by immediate responses to the supply of amino acids, present evidence together with results of others indicate that microsequestration could be linked to functional and quantitative alterations in the smooth endoplasmic reticulum. Both types of regulation contributed equally to the marked suppression of proteolysis during cytoplasmic regrowth.
肝细胞中的细胞质蛋白被两类溶酶体隔离并降解，即明显的自噬泡（巨自噬）和致密体（微自噬）。将每类中包含内化蛋白的表观空间体积，连同细胞质蛋白浓度的估计值，作为预测喂食、饥饿48小时和饥饿再喂食小鼠肝脏中溶酶体系统蛋白降解速率的基础。假设所有隔离蛋白的周转与先前在明显自噬泡中确定的周转相同（0.087分钟-1），我们在研究的三种条件下预测速率与观察速率之间获得了密切一致。然而，这两种自噬成分表现出不同的调节模式。微自噬在饥饿和再喂食过程中呈下降趋势，这一趋势充分解释了饥饿期间蛋白降解绝对速率的下降。相比之下，巨自噬在整个饥饿过程中保持恒定，但在再喂食时几乎被消除。虽然后者的调节在很大程度上可以通过对氨基酸供应的即时反应来解释，但现有证据以及其他研究结果表明，微隔离可能与滑面内质网的功能和数量改变有关。在细胞质再生过程中，这两种调节类型对蛋白水解的显著抑制作用相同。
