Activation of a selective pathway of lysosomal proteolysis in rat
liver by prolonged starvation.
Cuervo, Ana Maria, Erwin Knecht, Stanley R. Terlecky, and J. Fred
Dice.
Instituto de Investigaciones Citologicas, Amadeo de Saboya 4, 46010
Valencia, Spain and Department of Physiology, Tufts University School
of Medicine, 136 Harrison Avenue, Boston, MA 02111, Current Address:
Department of Biology, University of California at San Diego, La
Jolla, CA 92093
APStracts 2:0208C, 1995.
Lysosomal uptake and degradation of polypeptides such as
glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribonuclease A
(RNase A), and RNase S-peptide (residues 1-20 of RNase A) are
progressively activated in rat liver by starvation prior to isolation
of lysosomes. This pathway of proteolysis is selective since it is
stimulated by the heat shock cognate protein of 73 kDa (hsc73) and
ATP/MgCl2, and lysosomal uptake of RNase A could be competed by GAPDH
but not by ovalbumin. A portion of intracellular hsc73 is associated
with certain lysosomes, and the amount of lysosomal hsc73 increases
by 5-10-fold during prolonged starvation. The lysosome-associated
hsc73 is primarily within the lysosomal lumen. Double immunogold
labeling of lysosomes incubated in vitro with RNase A detects this
protein substrate as well as hsc73 within lysosomes. More than two
-thirds of the labeled lysosomes contain both RNase A and hsc73. The
possible physiological significance of the activation of this
selective pathway of lysosomal proteolysis in long-term starvation is
discussed.
Received 13 December 1994; accepted in final form 12 May 1995.
APS Manuscript Number C716-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.