UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Inhibition of Mitochondrial Complex I Impairs Release of α-Galactosidase by Jurkat Cells

Lambert, JRA; Howe, SJ; Rahim, AA; Burke, DG; Heales, SJR; (2019) Inhibition of Mitochondrial Complex I Impairs Release of α-Galactosidase by Jurkat Cells. International Journal of Molecular Sciences , 20 (18) , Article 4349. 10.3390/ijms20184349. Green open access

[thumbnail of Heales ijms-20-04349-v2.pdf]
Preview
Text
Heales ijms-20-04349-v2.pdf - Published Version

Download (1MB) | Preview

Abstract

Fabry disease (FD) is caused by mutations in the GLA gene that encodes lysosomal α-galactosidase-A (α-gal-A). A number of pathogenic mechanisms have been proposed and these include loss of mitochondrial respiratory chain activity. For FD, gene therapy is beginning to be applied as a treatment. In view of the loss of mitochondrial function reported in FD, we have considered here the impact of loss of mitochondrial respiratory chain activity on the ability of a GLA lentiviral vector to increase cellular α-gal-A activity and participate in cross correction. Jurkat cells were used in this study and were exposed to increasing viral copies. Intracellular and extracellular enzyme activities were then determined; this in the presence or absence of the mitochondrial complex I inhibitor, rotenone. The ability of cells to take up released enzyme was also evaluated. Increasing transgene copies was associated with increasing intracellular α-gal-A activity but this was associated with an increase in Km. Release of enzyme and cellular uptake was also demonstrated. However, in the presence of rotenone, enzyme release was inhibited by 37%. Excessive enzyme generation may result in a protein with inferior kinetic properties and a background of compromised mitochondrial function may impair the cross correction process.

Type: Article
Title: Inhibition of Mitochondrial Complex I Impairs Release of α-Galactosidase by Jurkat Cells
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms20184349
Publisher version: https://doi.org/10.3390/ijms20184349
Language: English
Additional information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Keywords: mitochondria; Fabry; cross correction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10081632
Downloads since deposit
69Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item