Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Human NARP Mitochondrial Mutation Metabolism Corrected With α-Ketoglutarate/Aspartate

Human NARP Mitochondrial Mutation Metabolism Corrected With α-Ketoglutarate/Aspartate ORIGINAL CONTRIBUTION Human NARP Mitochondrial Mutation Metabolism Corrected With -Ketoglutarate/Aspartate A Potential New Therapy Gianluca Sgarbi, PhD; Gabriella A. Casalena, PhD; Alessandra Baracca, PhD; Giorgio Lenaz, MD, PhD; Salvatore DiMauro, MD; Giancarlo Solaini, PhD Objective: To verify whether enhanced substrate-level tion by exposure to the ionophore gramicidin or were en- phosphorylation increases viability and adenosine 5- ergy challenged by oligomycin inhibition, their survival at triphosphate (ATP) content of cells with neuropathy, 72 hours was 5%, but this increased to 70% when the me- ataxia, and retinitis pigmentosa/maternally inherited Leigh dium was supplemented with-ketoglutarate/aspartate to syndrome (NARP/MILS) mitochondrial DNA muta- boost mitochondrial substrate-level phosphorylation. Ho- tions and ATP synthase dysfunction. moplasmic cybrids harboring the 8993T→G NARP mu- tation were also protected from death (75% vs 15% sur- Design: We used cell lines “poisoned” with oligomy- vival at 72 hours) by the supplemented medium and their cin, the specific inhibitor of ATP synthase, and “natu- ATP content was similar to controls. ral” models, including transmitochondrial human cell lines (cybrids) harboring 2 different pathogenic muta- Conclusions: These results show that ATP synthase– tions associated with the NARP/MILS phenotypes. deficient cells can be rescued by increasing mitochondrial substrate-level phosphorylation and suggest potential di- http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Neurology American Medical Association

Human NARP Mitochondrial Mutation Metabolism Corrected With α-Ketoglutarate/Aspartate

Download PDF
7 pages

Loading next page...
 
/lp/american-medical-association/human-narp-mitochondrial-mutation-metabolism-corrected-with-FiUD55e5KC

References (35)

Publisher
American Medical Association
Copyright
Copyright 2009 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6149
eISSN
2168-6157
DOI
10.1001/archneurol.2009.134
pmid
19667215
Publisher site
See Article on Publisher Site

Abstract

ORIGINAL CONTRIBUTION Human NARP Mitochondrial Mutation Metabolism Corrected With -Ketoglutarate/Aspartate A Potential New Therapy Gianluca Sgarbi, PhD; Gabriella A. Casalena, PhD; Alessandra Baracca, PhD; Giorgio Lenaz, MD, PhD; Salvatore DiMauro, MD; Giancarlo Solaini, PhD Objective: To verify whether enhanced substrate-level tion by exposure to the ionophore gramicidin or were en- phosphorylation increases viability and adenosine 5- ergy challenged by oligomycin inhibition, their survival at triphosphate (ATP) content of cells with neuropathy, 72 hours was 5%, but this increased to 70% when the me- ataxia, and retinitis pigmentosa/maternally inherited Leigh dium was supplemented with-ketoglutarate/aspartate to syndrome (NARP/MILS) mitochondrial DNA muta- boost mitochondrial substrate-level phosphorylation. Ho- tions and ATP synthase dysfunction. moplasmic cybrids harboring the 8993T→G NARP mu- tation were also protected from death (75% vs 15% sur- Design: We used cell lines “poisoned” with oligomy- vival at 72 hours) by the supplemented medium and their cin, the specific inhibitor of ATP synthase, and “natu- ATP content was similar to controls. ral” models, including transmitochondrial human cell lines (cybrids) harboring 2 different pathogenic muta- Conclusions: These results show that ATP synthase– tions associated with the NARP/MILS phenotypes. deficient cells can be rescued by increasing mitochondrial substrate-level phosphorylation and suggest potential di-

Journal

JAMA Neurology – American Medical Association

Published: Aug 1, 2009

There are no references for this article.