Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies

Abstract

In leukocytes, alteration in the copy number of mtDNA is related to the proportion of mtDNA with a point mutation or large-scale deletion, which may serve as a biomarker in the pathogenesis and disease progression of MELAS and MERRF syndromes.

The Cross-Talk Between Mitochondria and the Nucleus in the Response to Oxidative Stress Associated with Mitochondrial Dysfunction in Mitochondrial Encephalomyopathies

“…Recently, Folbergrová et al (2010) reported that the persistent inhibition of Complex I led to the overproduction of ROS, which could contribute to the neuronal injury in a rat model of seizures and in the patients with epileptogene s i s . I n a p r e v i o u s s t u d y , w e o b s e r v e d a significant decrease in the copy number of mtDNA in the leukocytes of patients with mitochondrial encephalomyopathies including MERRF and MELAS syndromes, respectively (Liu et al, 2006). The amplitude of change was related to the proportion of mutant mtDNA, which may serve as a biomarker in the pathogenesis and progression of the mitochondrial diseases.…”

Altitude can alter the mtDNA copy number and nDNA integrity in sperm

“…Therefore, the genetic alteration of mtDNA will directly impact on the function of the OXPHOS, and may ultimately cause fertility problems [3]. The copy number of mtDNA (i.e., the number of mtDNA per spermatozoon) is one of the major mitochondrial genetic features, and plays a critical role in mtDNA-mediated pathological pathways [4][5][6][7]. For example, in infertile men with abnormal sperm quality, mtDNA content was found to be significantly increased, and could serve as a marker for spermatogenic dysfunction [8].…”

Prenatal Environmental Exposure and Neurodevelopmentally Important Gene Expression in Malformed Brain Tissue from Pediatric Intractable Epilepsy Patients

“…mtDNA mutations often result in respiratory chain defects resulting in decreased ATP production, enhanced ROS and free radical production in mitochondria. Mitochondrial dysfunction or cell apoptosis result upon the decline in the copy number of mtDNA or the accumulation oxidative damage and mtDNA mutations reaches a critical point, thus, resulting in defective energy metabolism of the target tissues (Liu et al, 2006). Alteration of mtDNA copy number in affected copy numbers has been suggested play a role in the pathogenesis and progression of mitochondrial diseases (Liu et al, 2006;Park et al, 2009).…”

“…Mitochondrial dysfunction or cell apoptosis result upon the decline in the copy number of mtDNA or the accumulation oxidative damage and mtDNA mutations reaches a critical point, thus, resulting in defective energy metabolism of the target tissues (Liu et al, 2006). Alteration of mtDNA copy number in affected copy numbers has been suggested play a role in the pathogenesis and progression of mitochondrial diseases (Liu et al, 2006;Park et al, 2009). Studies have documented the presence of inheritable copy number variations (CNVs) in the human genome, and copy number aberrations (CNAs), which are acquired somatic alterations, have been observed in tumor tissues (Sun et al, 2009;Zhang et al, 2010).…”

“…According to Liu et al (2006), the number of mitochondria per cell is maintained within a constant range in response to the energy need of the cell to maintain normal physiologic functions. mtDNA mutations often result in respiratory chain defects resulting in decreased ATP production, enhanced ROS and free radical production in mitochondria.…”