Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity.

TitleTissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity.
Publication TypeJournal Article
Year of Publication2015
AuthorsD'Erchia, AMaria, Atlante, A, Gadaleta, G, Pavesi, G, Chiara, M, De Virgilio, C, Manzari, C, Mastropasqua, F, Prazzoli, GMarco, Picardi, E, Gissi, C, Horner, D, Reyes, A, Sbisà, E, Tullo, A, Pesole, G
JournalMitochondrion
Volume20
Pagination13-21
Date Published2015 Jan
ISSN1872-8278
KeywordsCell Respiration, DNA, Mitochondrial, Exome, Gene Dosage, Humans, Male, Middle Aged, Mitochondria, Transcription, Genetic
Abstract

Eukaryotic cells contain a population of mitochondria, variable in number and shape, which in turn contain multiple copies of a tiny compact genome (mtDNA) whose expression and function is strictly coordinated with the nuclear one. mtDNA copy number varies between different cell or tissues types, both in response to overall metabolic and bioenergetics demands and as a consequence or cause of specific pathological conditions. Here we present a novel and reliable methodology to assess the effective mtDNA copy number per diploid genome by investigating off-target reads obtained by whole-exome sequencing (WES) experiments. We also investigate whether and how mtDNA copy number correlates with mitochondrial mass, respiratory activity and expression levels. Analyzing six different tissues from three age- and sex-matched human individuals, we found a highly significant linear correlation between mtDNA copy number estimated by qPCR and the frequency of mtDNA off target WES reads. Furthermore, mtDNA copy number showed highly significant correlation with mitochondrial gene expression levels as measured by RNA-Seq as well as with mitochondrial mass and respiratory activity. Our methodology makes thus feasible, at a large scale, the investigation of mtDNA copy number in diverse cell-types, tissues and pathological conditions or in response to specific treatments.

DOI10.1016/j.mito.2014.10.005
Alternate JournalMitochondrion
Citation Key10.1016/j.mito.2014.10.005
PubMed ID25446395