Hepatocytic autophagy.
Autophagy is a non-selective bulk process for degradation of cytoplasm, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lifes. The initial autophagic sequestration step is subject to feedback inhibition by amino acids, an effect which is potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive, alpha 1-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid. Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy in a differential (ligand-dependent) manner, and that amphisomes may play a central role as collecting stations for material destined for lysosomal degradation.
Seglen
P O
PO
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.
Gordon
P B
PB
Holen
I
I
Høyvik
H
H
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001216:Asparagine / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects; D008561:Membrane Fusion / Q000187:drug effects; D008854:Microscopy, Electron; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism
D000596:Amino Acids; D006728:Hormones; D011506:Proteins; D001216:Asparagine; D000242:Cyclic AMP