Induction of autophagy by amino-acid deprivation in perfused rat liver

GE Mortimore, CM Schworer - Nature, 1977 - nature.com
GE Mortimore, CM Schworer
Nature, 1977nature.com
AUTOPHAGOCYTOSIS is generally regarded as an important mechanism for ridding the cell
of injured or unwanted cytoplasmic constituents and for degrading normal components in
response to energy needs1, 2. Autophagy has been noted in HeLa cells deprived of foetal
calf serum and amino acids3. It has also been seen in rat liver after glucagon
administration4, 5, during nutritional deprivation7, 8 and in diabetes9, 10. Thus autophagy
could have a physiological role in the maintenance of body amino acid pools, although there …
Abstract
AUTOPHAGOCYTOSIS is generally regarded as an important mechanism for ridding the cell of injured or unwanted cytoplasmic constituents and for degrading normal components in response to energy needs1,2. Autophagy has been noted in HeLa cells deprived of foetal calf serum and amino acids3. It has also been seen in rat liver after glucagon administration4, 5, during nutritional deprivation7, 8 and in diabetes9, 10. Thus autophagy could have a physiological role in the maintenance of body amino acid pools, although there is no direct experimental evidence for this. We reported previously that rates of proteolysis, and lysosomal sizes are seen to increase when rat livers are cyclically perfused with an unsupplemented medium and decrease in response to added amino acids11–13. We strongly suspected that autophagy was the underlying event, but the nature of the process has been difficult to define12. The possibility was considered that its expression was self-limited by the accumulation of amino acids from endogenous proteolysis. We now show that when this accumulation is prevented by perfusing livers in the single-pass mode, autophagic changes appear that are morphologically indistinguishable from those occurring after maximal doses of glucagon4–6.
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