Iodothyronine deiodinase structure and function: from ascidians to humans

Area of Science:

• Biochemistry
• Endocrinology
• Evolutionary Biology

Background:

• Iodothyronine deiodinases are crucial enzymes mediating thyroid hormone (TH) action.
• These enzymes catalyze the production and degradation of 3,5,3'-triiodothyronine (T(3)) through outer and inner ring deiodination.
• Three distinct types (D1, D2, D3) are found in vertebrates, sharing a selenocysteine residue but exhibiting type-specific differences.

Purpose of the Study:

• To review the characteristics and evolutionary conservation of iodothyronine deiodinases (D1, D2, D3).
• To explore their impact on systemic and intracellular T(3) availability across different species, developmental stages, and tissues.
• To examine their response to thyroid status and their presence in lower chordates and invertebrates.

Main Methods:

• Comparative analysis of deiodinase characteristics, including Km, inhibitor sensitivity, and cofactor dependence.
• Review of expression and activity patterns in response to thyroid status.
• Examination of deiodinase sequences in lower chordates and invertebrate genomes.

Main Results:

• D2 and D3 show conserved characteristics, while D1 exhibits greater evolutionary diversity.
• All three deiodinase types influence systemic T(3) levels and intracellular T(3) availability, with contributions varying by species and tissue.
• D2 and D3 expression/activity respond oppositely to thyroid status, while D1 response is variable.
• Selenodeiodinases exist in urochordates and cephalochordates, and amphioxus possesses a non-selenodeiodinase.
• Deiodinase-like sequences are found in non-deuterostomes, suggesting broad invertebrate relevance.

Conclusions:

• Iodothyronine deiodinases play diverse roles in thyroid hormone metabolism, with significant evolutionary variation.
• Their differential expression and activity are critical for tissue-specific thyroid hormone availability.
• The presence of deiodinase-like sequences in invertebrates suggests ancient origins and widespread functional importance of TH deiodination.