Mitochondrial DNA (mtDNA) is a small fraction of our hereditary material. However, this molecule has had an overwhelming presence in scientific research for decades until the arrival high-throughput studies. Several appealing properties justify application mtDNA to understand how human populations are—from genetic perspective—and individuals exhibit phenotypes biomedical importance. Here, I rev...

The human mitochondrial genome is replicated by DNA polymerase γ in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS...

Quantitative real-time PCR has become a popular method to analyze and quantify changes in the copy number of mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) is often used as an endogenous reference for mtDNA abundance. In our experience, using nDNA as a reference is problematic, due to differences in the extraction efficiency of nDNA and mtDNA and variation in the ploidy of experimental sampl...

BACKGROUND The extent to which mitochondrial DNA (mtDNA) content (also termed mtDNA copy number) in normal human cells is influenced by genetic factors has yet to be established. In addition, whether inherited variation of mtDNA content in normal cells contributes to cancer susceptibility remains unclear. Renal cell carcinoma accounts for 85% of all renal cancers. No studies have investigated t...

Mutation and reduction of mitochondrial DNA (mtDNA) have been suggested as factors in the pathogenesis of several metabolic diseases. Recently, we demonstrated that C1qTNF-related protein-6 (CTRP6) is involved in fatty acid metabolism in muscle cells. In this study, we showed that expression of CTRP6 was up-regulated in mtDNA-depleted C2C12 cells, which displayed a marked decrease in cellular m...

Using in situ hybridization and immunocytochemistry, we studied a muscle biopsy sample from a patient with Kearns-Sayre syndrome (KSS) who had a deletion of mitochondrial DNA (mtDNA) and partial deficiency of cytochrome-c oxidase (COX; EC 1.9.3.1). We sought a relationship between COX deficiency and abnormalities of mtDNA at the single-fiber level. COX deficiency clearly correlated with a decre...

Accurate and reliable quantification of the abundance of mitochondrial DNA (mtDNA) molecules, both wild-type and those harbouring pathogenic mutations, is important not only for understanding the progression of mtDNA disease but also for evaluating novel therapeutic approaches. A clear understanding of the sensitivity of mtDNA measurement assays under different experimental conditions is theref...

Regulation of mammalian mtDNA gene expression is critical for altering oxidative phosphorylation capacity in response to physiological demands and disease processes. The basal machinery for initiation of mtDNA transcription has been molecularly defined, but the mechanisms regulating its activity are poorly understood. In this study, we show that MTERF3 is a negative regulator of mtDNA transcrip...

Organismal fitness requires functional integration of nuclear and mitochondrial genomes. Structural and regulatory elements coevolve within lineages and several studies have found that interpopulation hybridization disrupts mitonuclear interactions. Because mitochondrial RNA polymerase (mtRPOL) plays key roles in both mitochondrial DNA (mtDNA) replication and transcription, the interaction betw...