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

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...

Full description

Saved in:

Bibliographic Details
Published in:	G3 : genes - genomes - genetics Vol. 10; no. 5; pp. 1599 - 1612
Main Authors:	Sejour, Richard, Sanguino, Roger A, Mikolajczak, Monika, Ahmadi, Walishah, Villa-Cuesta, Eugenia
Format:	Journal Article
Language:	English
Published:	England Genetics Society of America 01-05-2020 Oxford University Press
Subjects:	Animals coevolution mtdna/ndna DNA, Mitochondrial - genetics Drosophila - drug effects Drosophila - genetics Drosophila melanogaster - drug effects Drosophila melanogaster - genetics Drosophila Proteins - genetics Haplotypes Investigations Mitochondria - genetics Oxidative Stress Phenotype Sirolimus - pharmacology sirt4 Sirtuins - genetics tor pathway TOR pathway coevolution mtDNA/nDNA Sirt4
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 strains containing mtDNA and nDNA with ( -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 and mtDNA haplotypes display opposite Sirt4-mediated phenotypes in the regulation of whole-fly oxygen consumption. Moreover, our data reflect that the deletion of rescued the metabolic response to rapamycin among the introgressed strains. We propose that Sirt4 is a suitable candidate for studying the properties of mitochondrial-nuclear epistasis in modulating mitochondrial metabolism.
Bibliography:	Present address: Department of Pharmacological Sciences, Stony Brook School of Medicine. Present address: NYU College of Dentistry. Present address: Poznan University of Medical Sciences.
ISSN:	2160-1836 2160-1836
DOI:	10.1534/g3.120.401174