Characterization of complex III deficiency and liver dysfunction in GRACILE syndrome caused by a BCS1L mutation.

Abstract

A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondrial membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex III, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction.

• Authors: Heike Kotarsky, Riitta Karikoski, Matthias Mörgelin, Sanna Marjavaara, Petra Bergman, De-Liang Zhang, Joél Smet, Rudy van Coster, Vineta Fellman
• Journal: Mitochondrion (Mitochondrion) Vol. 10 Issue 5 Pg. 497-509 (Aug 2010) ISSN: 1872-8278 [Electronic] Netherlands
• PMID: 20580947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Mitochondria Research Society. All rights reserved.

Chemical References

• BCS1L protein, human
• HEPH protein, human
• Membrane Proteins
• Ferritins
• Iron
• Ceruloplasmin
• ATPases Associated with Diverse Cellular Activities
• Electron Transport Complex III

Topics

• ATPases Associated with Diverse Cellular Activities
• Ceruloplasmin (metabolism)
• Congenital Abnormalities (pathology)
• Electron Transport Complex III (deficiency, metabolism)
• Female
• Ferritins (metabolism)
• Histocytochemistry
• Humans
• Infant
• Infant, Newborn
• Iron (metabolism)
• Kidney (pathology)
• Liver (pathology)
• Liver Diseases
• Membrane Proteins (metabolism)
• Myocardium (pathology)
• Placenta (pathology)
• Pregnancy
• Up-Regulation