title: Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity.
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.
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Erchia
authors.affiliation: Istituto di Biomembrane e Bioenergetica, CNR, via Amendola 165/A, Bari 70126, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Atlante
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Gadaleta
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Pavesi
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Chiara
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: De Virgilio
authors.affiliation: Istituto di Biomembrane e Bioenergetica, CNR, via Amendola 165/A, Bari 70126, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Manzari
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mastropasqua
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Prazzoli
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Picardi
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Gissi
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milano 20133, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Horner
authors.affiliation: Mitochondrial Biology Unit, Medical Research Council, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, United Kingdom.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Reyes
authors.affiliation: Istituto di Tecnologie Biomediche- Sede di Bari, CNR, Via Amendola 122/D, Bari 70126, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sbisà
authors.affiliation: Istituto di Tecnologie Biomediche- Sede di Bari, CNR, Via Amendola 122/D, Bari 70126, Italy.
authors.forename: Apollonia
authors.initials: A
authors.lastname: Tullo
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, Bari 70126, Italy; Istituto di Biomembrane e Bioenergetica, CNR, via Amendola 165/A, Bari 70126, Italy. Electronic address: graziano.pesole@uniba.it.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
mesh_terms: D019069:Cell Respiration; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics; D059472:Exome; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial
keywords: Bioinformatics tools; Mitochondrial DNA; Mitochondrial activity; Mitochondrial gene expression; Nucleo-mitochondrial cross-talk; Whole-exome sequencing