Cargando…

Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes

Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of bio...

Descripción completa

Detalles Bibliográficos
Autor principal: Cronan, John E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253636/
https://www.ncbi.nlm.nih.gov/pubmed/32508887
http://dx.doi.org/10.3389/fgene.2020.00510
_version_ 1783539370915004416
author Cronan, John E.
author_facet Cronan, John E.
author_sort Cronan, John E.
collection PubMed
description Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of biochemical analysis at the enzyme level. An exception was the LIPT1 protein for which a perplexing property had been reported, a ligase lacking the ability to activate its substrate. This led to several models, some contradictory, to accommodate the role of LIPT1 protein activity in explaining the phenotypes of the afflicted neonatal patients. Recent evidence indicates that this LIPT1 protein activity is a misleading evolutionary artifact and that the physiological role of LIPT1 is in transfer of lipoic acid moieties from one protein to another. This and other new biochemical data now define a straightforward pathway that fully explains each of the human disorders specific to the assembly of lipoic acid on its cognate enzyme proteins.
format Online
Article
Text
id pubmed-7253636
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-72536362020-06-05 Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes Cronan, John E. Front Genet Genetics Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of biochemical analysis at the enzyme level. An exception was the LIPT1 protein for which a perplexing property had been reported, a ligase lacking the ability to activate its substrate. This led to several models, some contradictory, to accommodate the role of LIPT1 protein activity in explaining the phenotypes of the afflicted neonatal patients. Recent evidence indicates that this LIPT1 protein activity is a misleading evolutionary artifact and that the physiological role of LIPT1 is in transfer of lipoic acid moieties from one protein to another. This and other new biochemical data now define a straightforward pathway that fully explains each of the human disorders specific to the assembly of lipoic acid on its cognate enzyme proteins. Frontiers Media S.A. 2020-05-21 /pmc/articles/PMC7253636/ /pubmed/32508887 http://dx.doi.org/10.3389/fgene.2020.00510 Text en Copyright © 2020 Cronan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Cronan, John E.
Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title_full Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title_fullStr Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title_full_unstemmed Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title_short Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
title_sort progress in the enzymology of the mitochondrial diseases of lipoic acid requiring enzymes
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253636/
https://www.ncbi.nlm.nih.gov/pubmed/32508887
http://dx.doi.org/10.3389/fgene.2020.00510
work_keys_str_mv AT cronanjohne progressintheenzymologyofthemitochondrialdiseasesoflipoicacidrequiringenzymes