SUBCELLULAR-LOCALIZATION OF THE FORMATION OF TRIIODOTHYRONINE IN THE RABBIT RENAL PROXIMAL TUBULE

Type I 5'-deiodinase (5'-DI) is responsible for the conversion of L-thyroxine (T4) to 3,3',5-L-triiodothyronine (T3), the active form of the thyroid hormone. High 5'-DI activity is known to exist in proximal renal cells, but the subcellular localization of this enzyme is still controversial. We have reinvestigated the subcellular distribution of this enzyme in freshly prepared rabbit proximal renal cells. When the homogenate was separated into brush borders, basolateral membranes, endoplasmic reticulum, mitochondria and lysosomes, the 5'-DI activity showed an endoplasmic reticulum location. Any 5'-DI activity in the other membrane fractions could be accounted for by contamination with endoplasmic reticulum. Detergent treatment of endoplasmic reticulum vesicles had no effect on 5'-DI activity under conditions in which mannose-6-phosphatase (a lumenal marker) was increased 3-fold. We conclude that 5'-DI, or at least its active site, is located at the cytosolic surface of the endoplasmic reticulum and that this organelle plays a major role in the formation of T3 from T4 by renal proximal cells.