Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity

PloS One
Alberto Cruz-BermúdezMiguel Ángel Fernández-Moreno

Abstract

The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.

References

Oct 1, 1992·Biochemical Medicine and Metabolic Biology·B H RobinsonD C Wallace
Feb 1, 1995·Journal of Medical Genetics·P Riordan-Eva, A E Harding
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·A M MoudyS M Rothman
Mar 5, 1999·Science·D C Wallace
May 29, 1999·The Journal of Biological Chemistry·A Barrientos, C T Moraes
Oct 9, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mayte MonteroJavier Alvarez
Dec 5, 2002·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Neil HowellIwona Kubacka
Jul 30, 2004·Biochimica Et Biophysica Acta·Giorgio LenazGiancarlo Solaini
Oct 25, 2008·Methods : a Companion to Methods in Enzymology·Maria Antonietta CalvarusoLeo Nijtmans
Nov 5, 2008·Journal of Bioenergetics and Biomembranes·Volker ZickermannUlrich Brandt
Nov 13, 2008·Journal of Medical Genetics·P Yu-Wai-ManP F Chinnery
Nov 19, 2008·European Journal of Medical Genetics·Atle MelbergAnders Oldfors
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Mar 9, 2010·Brain : a Journal of Neurology·Andrew J TrevelyanDoug M Turnbull
May 28, 2010·Nature·Rouslan G EfremovLeonid A Sazanov
Aug 10, 2010·Biochemical and Biophysical Research Communications·Juanjuan ZhangMin-Xin Guan
Nov 30, 2010·Progress in Retinal and Eye Research·Patrick Yu-Wai-ManPatrick F Chinnery
May 14, 2011·Biochimica Et Biophysica Acta·Ulrich Brandt
Sep 3, 2011·Current Genomics·E Kirches
Sep 3, 2011·PLoS Biology·Stefan DröseUlrich Brandt
Sep 20, 2011·Biochimica Et Biophysica Acta·Masakazu MimakiMichael T Ryan
Dec 14, 2011·IUBMB Life·Andrew P Halestrap, Marieangela C Wilson
Feb 22, 2012·Cell Metabolism·David Moreno-LastresCristina Ugalde
Jun 26, 2012·Advances in Experimental Medicine and Biology·Daniele Ghezzi, Massimo Zeviani
Mar 27, 2013·Annual Review of Biochemistry·Judy Hirst
Apr 16, 2013·Antioxidants & Redox Signaling·Evelina MaranzanaMaria Luisa Genova
Jul 3, 2013·Science·Esther Lapuente-BrunJosé Antonio Enríquez

❮ Previous
Next ❯

Citations

Apr 2, 2020·Cells·Andrea Dalmao-FernándezMercedes Fernández-Moreno
Aug 1, 2020·Investigative Ophthalmology & Visual Science·Sarah J WassmerCatherine Tsilfidis
May 25, 2021·Frontiers in Molecular Biosciences·Olga A ZhuninaAlexander N Orekhov
Aug 25, 2021·Nucleic Acids Research·Thiloka E RatnaikePatrick F Chinnery
Jul 19, 2017·Mitochondrion·Leonardo CaporaliValerio Carelli

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
electrophoresis
Protein Assay
flow cytometry

Software Mentioned

MITOMAP
MXP

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved