Cargando…

Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8

Chronic loss of Augmenter of Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; however, the mechanism for this disorder remains unclear. Here, we demonstrate that loss of ALR, a principal component of the MIA40/ALR protein import pathway, results in impaired cytosolic Fe/S c...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Hsiang-Chun, Shapiro, Jason Solomon, Jiang, Xinghang, Senyei, Grant, Sato, Teruki, Geier, Justin, Sawicki, Konrad T, Ardehali, Hossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055271/
https://www.ncbi.nlm.nih.gov/pubmed/33835027
http://dx.doi.org/10.7554/eLife.65158
_version_ 1783680419501178880
author Chang, Hsiang-Chun
Shapiro, Jason Solomon
Jiang, Xinghang
Senyei, Grant
Sato, Teruki
Geier, Justin
Sawicki, Konrad T
Ardehali, Hossein
author_facet Chang, Hsiang-Chun
Shapiro, Jason Solomon
Jiang, Xinghang
Senyei, Grant
Sato, Teruki
Geier, Justin
Sawicki, Konrad T
Ardehali, Hossein
author_sort Chang, Hsiang-Chun
collection PubMed
description Chronic loss of Augmenter of Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; however, the mechanism for this disorder remains unclear. Here, we demonstrate that loss of ALR, a principal component of the MIA40/ALR protein import pathway, results in impaired cytosolic Fe/S cluster biogenesis in mammalian cells. Mechanistically, MIA40/ALR facilitates the mitochondrial import of ATP-binding cassette (ABC)-B8, an inner mitochondrial membrane protein required for cytoplasmic Fe/S cluster maturation, through physical interaction with ABCB8. Downregulation of ALR impairs mitochondrial ABCB8 import, reduces cytoplasmic Fe/S cluster maturation, and increases cellular iron through the iron regulatory protein-iron response element system. Our finding thus provides a mechanistic link between MIA40/ALR import machinery and cytosolic Fe/S cluster maturation through the mitochondrial import of ABCB8, and offers a potential explanation for the pathology seen in patients with ALR mutations.
format Online
Article
Text
id pubmed-8055271
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-80552712021-04-22 Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8 Chang, Hsiang-Chun Shapiro, Jason Solomon Jiang, Xinghang Senyei, Grant Sato, Teruki Geier, Justin Sawicki, Konrad T Ardehali, Hossein eLife Cell Biology Chronic loss of Augmenter of Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; however, the mechanism for this disorder remains unclear. Here, we demonstrate that loss of ALR, a principal component of the MIA40/ALR protein import pathway, results in impaired cytosolic Fe/S cluster biogenesis in mammalian cells. Mechanistically, MIA40/ALR facilitates the mitochondrial import of ATP-binding cassette (ABC)-B8, an inner mitochondrial membrane protein required for cytoplasmic Fe/S cluster maturation, through physical interaction with ABCB8. Downregulation of ALR impairs mitochondrial ABCB8 import, reduces cytoplasmic Fe/S cluster maturation, and increases cellular iron through the iron regulatory protein-iron response element system. Our finding thus provides a mechanistic link between MIA40/ALR import machinery and cytosolic Fe/S cluster maturation through the mitochondrial import of ABCB8, and offers a potential explanation for the pathology seen in patients with ALR mutations. eLife Sciences Publications, Ltd 2021-04-09 /pmc/articles/PMC8055271/ /pubmed/33835027 http://dx.doi.org/10.7554/eLife.65158 Text en © 2021, Chang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Chang, Hsiang-Chun
Shapiro, Jason Solomon
Jiang, Xinghang
Senyei, Grant
Sato, Teruki
Geier, Justin
Sawicki, Konrad T
Ardehali, Hossein
Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title_full Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title_fullStr Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title_full_unstemmed Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title_short Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8
title_sort augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of atp-binding cassette b8
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055271/
https://www.ncbi.nlm.nih.gov/pubmed/33835027
http://dx.doi.org/10.7554/eLife.65158
work_keys_str_mv AT changhsiangchun augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT shapirojasonsolomon augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT jiangxinghang augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT senyeigrant augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT satoteruki augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT geierjustin augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT sawickikonradt augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8
AT ardehalihossein augmenterofliverregenerationregulatescellularironhomeostasisbymodulatingmitochondrialtransportofatpbindingcassetteb8