کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1902507 1045753 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Somatic mutations of mitochondrial DNA in aging and cancer progression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Somatic mutations of mitochondrial DNA in aging and cancer progression
چکیده انگلیسی

Mitochondria are intracellular organelles responsible for generating ATP through respiration and oxidative phosphorylation (OXPHOS), producing reactive oxygen species, and initiating and executing apoptosis. Mitochondrial dysfunction has been observed to be an important hallmark of aging and cancer. Because mitochondrial DNA (mtDNA) is important in maintaining functionally competent organelles, accumulation of mtDNA mutations can affect energy production, oxidative stress, and cell survival, which may contribute to aging and/or carcinogenesis. This review outlines a variety of somatic mtDNA mutations identified in aging tissues and human cancers, as well as recent advances in understanding the causal role of mtDNA mutations in the aging process and cancer progression. Mitochondrial dysfunction elicited by somatic mutations in mtDNA could induce apoptosis in aging cells and some cancer cells with severe mtDNA mutations. In addition, it could activate mitochondria-to-nucleus retrograde signaling to modulate the expression of nuclear genes involved in a metabolic shift from OXPHOS to glycolysis, facilitate cells to adapt to altered environments and develop resistance to chemotherapeutic agents, or promote metastatic properties of cancer cells. These findings suggest that accumulation of somatic mtDNA mutations is not only an important contributor to human aging but also plays a critical role in cancer progression.

Research highlights▶ Somatic mutations of mitochondrial DNA (mtDNA) are accumulated in ageing tissues and in cancers. ▶ Somatic mtDNA mutations can induce a premature aging phenotype in the mouse. ▶ Somatic mutations of mtDNA could affect tumorigenesis and cancer progression. ▶ Crosstalk between mitochondria and the nucleus is an important area for aging and cancer research.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Ageing Research Reviews - Volume 9, Supplement, November 2010, Pages S47–S58
نویسندگان
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