An A10398G mitochondrial DNA alteration is related to increased risk of breast cancer, and associates with Her2 positive receptor.

Breast cancer is the most common malignancy and the second leading cause of cancer deaths among women worldwide after lung cancer. Mitochondria play a central role in the regulation of cellular function, metabolism, and cell death in cancer cells. We aim to examine the mitochondrial polymorphisms of complex I in association with breast cancer in an Iranian cohort.This experimental study includes 53 patients with breast cancer and 35 healthy control patients. In addition, tumor-adjacent normal breast tissue was obtained from each patient. The DNA of the tissue cells was extracted and analyzed for complex I mutations using a PCR sequencing method. Our results show 94 mtDNA complex I variants in tumor tissues. A10398G was the most prevalent polymorphism and strongly correlated with Her2 receptor in tumor tissue samples. Mitochondrial DNA (mtDNA) mutations have been widely linked to the etiology of numerous disorders. The mtDNA mutations screening on A10398G along with other mutations might provide insight on the role of mitochondrial mutations in breast cancer.

Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder.

OBJECTIVES: The aetiology and molecular mechanisms of schizophrenia (SCZ) and paranoid personality disorder (PPD) are not yet clarified. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of SCZ and PPD. METHODS: mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 634 SCZ, 340 PPD patients and 528 non-psychiatric subjects using quantitative real-time PCR, and associated comprehensive psychiatric, neurological and biochemical assessments. RESULTS: Significant expression changes of 18 genes in SCZ patients and 11 genes in PPD patients were detected in mitochondrial complex I. Most of these genes were novel candidate genes for SCZ and PPD. Several correlations between mRNA levels and severity of symptoms, drug response, deficits in attention, working memory, executive functions and brain activities were found. CONCLUSIONS: Deregulations of both core and supernumerary subunits of complex I are involved in the aetiology of SCZ and PPD. These deregulations have effects on brain activity as well as disorder characteristics.