title: Mitochondrial respiratory gene expression is suppressed in many cancers.
abstract: The fundamental metabolic decision of a cell, the balance between respiration and fermentation, rests in part on expression of the mitochondrial genome (mtDNA) and coordination with expression of the nuclear genome (nuDNA). Previously we described mtDNA copy number depletion across many solid tumor types (Reznik et al., 2016). Here, we use orthogonal RNA-sequencing data to quantify mtDNA expression (mtRNA), and report analogously lower expression of mtRNA in tumors (relative to normal tissue) across a majority of cancer types. Several cancers exhibit a trio of mutually consistent evidence suggesting a drop in respiratory activity: depletion of mtDNA copy number, decreases in mtRNA levels, and decreases in expression of nuDNA-encoded respiratory proteins. Intriguingly, a minority of cancer types exhibit a drop in mtDNA expression but an increase in nuDNA expression of respiratory proteins, with unknown implications for respiratory activity. Our results indicate suppression of respiratory gene expression across many cancer types.
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Ed
authors.identifier: 0000-0002-6511-5947
authors.initials: E
authors.lastname: Reznik
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Konnor
authors.initials: K
authors.lastname: La
authors.affiliation: Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.|cBio Center, Dana-Farber Cancer Institute, Boston, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
mesh_terms: D019069:Cell Respiration; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial
keywords: cancer; cancer biology; computational biology; human; metabolism; mitochondria; mtDNA; mtRNA; respiration; systems biology