ATP-induced stimulation of the intralysosomal hydrolysis of thyroglobulin. Evidence for an ATP-driven proton pump in thyroid lysosomes.
It is commonly admitted that the intralysosomal hydrolysis of thyroglobulin, which promotes thyroid hormonal secretion, requires an acidic pH. As a consequence the mechanisms by which such an acidic pH is set-up and maintained present an acute physiological interest. In the present work the extent of the intralysosomal hydrolysis of thyroglobulin (amount of TCA-soluble radioiodine formed during incubations of isolated thyroid lysosomes) has been retained as an index for the intralysosomal pH. Incubations in highly concentrated (250 mM) alkaline buffer, preincubations at 0 degree C in the presence of alkaline buffers or of methylamine, and incubations in the presence of FCCP (protonophore which dissipates proton-gradients) induced alkalinization of the lysosomal matrix (significant inhibition of thyroglobulin degradation). Addition of ATP to the incubation medium was shown to prevent these alkalinizations and to re-establish the acidic intralysosomal pH (normal thyroglobulin degradation) every time it had been experimentally increased. These results argue in favour of the existence of an ATP-driven proton pump in the membranes of thyroid lysosomes.
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D013954:Thyroglobulin / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*
D008744:Methylamines; D011522:Protons; D013963:Thyroid Hormones; D000255:Adenosine Triphosphate; D013954:Thyroglobulin