Sirt4 Modulates Oxidative Metabolism and Sensitivity to Rapamycin Through Species-Dependent Phenotypes in Drosophila mtDNA Haplotypes.

G3 : Genes - Genomes - Genetics
Richard SejourEugenia Villa-Cuesta

Abstract

The endosymbiotic theory proposes that eukaryotes evolved from the symbiotic relationship between anaerobic (host) and aerobic prokaryotes. Through iterative genetic transfers, the mitochondrial and nuclear genomes coevolved, establishing the mitochondria as the hub of oxidative metabolism. To study this coevolution, we disrupt mitochondrial-nuclear epistatic interactions by using strains that have mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) from evolutionarily divergent species. We undertake a multifaceted approach generating introgressed Drosophila strains containing D. simulans mtDNA and D. melanogaster nDNA with Sirtuin 4 (Sirt4 )-knockouts. Sirt4 is a nuclear-encoded enzyme that functions, exclusively within the mitochondria, as a master regulator of oxidative metabolism. We exposed flies to the drug rapamycin in order to eliminate TOR signaling, thereby compromising the cytoplasmic crosstalk between the mitochondria and nucleus. Our results indicate that D. simulans and D. melanogaster mtDNA haplotypes display opposite Sirt4-mediated phenotypes in the regulation of whole-fly oxygen consumption. Moreover, our data reflect that the deletion of Sirt4 rescued the metabolic response to rapamycin among the introgressed str...Continue Reading

References

Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·D A Petrov, D L Hartl
Feb 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Wei J Gong, Kent G Golic
Jan 22, 2004·Nature Reviews. Genetics·Jeremy N TimmisWilliam Martin
Apr 8, 2004·Molecular Cell·Ronald A Butow, Narayan G Avadhani
Feb 3, 2005·Genome Research·Chuong B DoSerafim Batzoglou
Apr 26, 2007·Molecular Endocrinology·Hiroyasu YamamotoJohan Auwerx
Dec 12, 2007·Transplant International : Official Journal of the European Society for Organ Transplantation·Andreas GaumannEdward K Geissler
Nov 19, 2008·Annual Review of Plant Biology·Tatjana KleineDario Leister
Jun 6, 2009·Ageing Research Reviews·Lydia W S Finley, Marcia C Haigis
Dec 17, 2009·Biochimica Et Biophysica Acta·Ryan J O DowlingNahum Sonenberg
Jul 14, 2010·Evolution; International Journal of Organic Evolution·Kristi L MontoothDavid M Rand
Aug 6, 2010·The Journal of Biological Chemistry·Nargis NasrinLaura Bordone
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Dec 21, 2010·Bioinformatics·Klaus Peter Schliep
Mar 13, 2012·International Journal of Molecular Sciences·Helena PópuloPaula Soares
Apr 12, 2012·Nucleic Acids Research·Prathima Iengar
May 26, 2012·Frontiers in Physiology·S Michal Jazwinski, Andres Kriete
Dec 20, 2014·Cell·Rommel A MathiasIleana M Cristea
Jan 13, 2015·Evolutionary Bioinformatics Online·Muhammad Tariq PervezMuhammad Shoaib
Jul 15, 2015·Molecular Cell·Johannes Gregor Matthias RackIvan Ahel
Oct 7, 2015·Current Biology : CB·John M Archibald
Mar 14, 2017·Trends in Molecular Medicine·Robert A H van de VenMarcia C Haigis
Jan 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jason G WoodStephen L Helfand
Jul 18, 2018·Bioinformatics·Emmanuel Paradis, Klaus Schliep
Aug 31, 2018·FEMS Yeast Research·Nicoletta GuaragnellaSergio Giannattasio
Oct 24, 2018·Molecular Biology and Evolution·Guangchuang YuYi Guan

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

MSA
Rmisc
ProbCons
graphics
summarySE
phylotools
R
P Data Analysis
R Project for Statistical Computing ( R Core Team
Expedata

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.