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Mitochondrial defects in cancer.

Carew JS, Huang P - Mol. Cancer (2002)

Bottom Line: Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis.Defects in mitochondrial function have long been suspected to contribute to the development and progression of cancer.In this review article, we aim to provide a brief summary of our current understanding of mitochondrial genetics and biology, review the mtDNA alterations reported in various types of cancer, and offer some perspective as to the emergence of mtDNA mutations, their functional consequences in cancer development, and therapeutic implications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. jcarew@mdanderson.org

ABSTRACT
Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Defects in mitochondrial function have long been suspected to contribute to the development and progression of cancer. In this review article, we aim to provide a brief summary of our current understanding of mitochondrial genetics and biology, review the mtDNA alterations reported in various types of cancer, and offer some perspective as to the emergence of mtDNA mutations, their functional consequences in cancer development, and therapeutic implications.

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Related in: MedlinePlus

The mitochondrial electron transport chain complexes are encoded by two genetic systems: the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA). The mtDNA codes for 7 NADH dehydrogenase (ND) subunits for complex I, a cytochrome b for complex III, 3 cytochrome c oxidase (COX) subunits for complex IV, and 2 ATPase (ATPase6/8) for complex V. Complex II is solely encoded by nDNA. The solid arrows indicate the direction of electron flow in the respiration chain; dashed arrows indicate the flow of genetic information from mtDNA or nDNA to RNA to protein; the numbers indicate the actual number of protein subunits coded by each genetic system. Specific inhibitors of RNA transcription or protein translation with relative selectivity for each genetic system are indicated in blue.
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Figure 1: The mitochondrial electron transport chain complexes are encoded by two genetic systems: the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA). The mtDNA codes for 7 NADH dehydrogenase (ND) subunits for complex I, a cytochrome b for complex III, 3 cytochrome c oxidase (COX) subunits for complex IV, and 2 ATPase (ATPase6/8) for complex V. Complex II is solely encoded by nDNA. The solid arrows indicate the direction of electron flow in the respiration chain; dashed arrows indicate the flow of genetic information from mtDNA or nDNA to RNA to protein; the numbers indicate the actual number of protein subunits coded by each genetic system. Specific inhibitors of RNA transcription or protein translation with relative selectivity for each genetic system are indicated in blue.

Mentions: The most well-known and best-characterized function of mitochondria is the production of adenosine triphosphate (ATP) through oxidative phosphorylation. This process is accomplished by a series of protein complexes, collectively known as the respiratory chain, encoded by both nDNA and mtDNA. The complete respiratory chain contains at least 87 polypeptides, 13 of which are encoded by mtDNA. Hence, the majority of the respiratory chain components are nuclear-encoded and imported into mitochondria after their translation in the cytosol (Figure 1). Thus, oxidative phosphorylation is a unique biochemical process achieved by a well-coordinated effort of the protein products from two separate genomes (nuclear and mitochondrial) working in concert within the same cells. However, this process is not absolutely required to fulfill cellular energy requirements. Glycolysis can also generate ATP and provides a compensatory mechanism when oxidative phosphorylation becomes inefficient as a consequence of defects in the respiratory chain.


Mitochondrial defects in cancer.

Carew JS, Huang P - Mol. Cancer (2002)

The mitochondrial electron transport chain complexes are encoded by two genetic systems: the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA). The mtDNA codes for 7 NADH dehydrogenase (ND) subunits for complex I, a cytochrome b for complex III, 3 cytochrome c oxidase (COX) subunits for complex IV, and 2 ATPase (ATPase6/8) for complex V. Complex II is solely encoded by nDNA. The solid arrows indicate the direction of electron flow in the respiration chain; dashed arrows indicate the flow of genetic information from mtDNA or nDNA to RNA to protein; the numbers indicate the actual number of protein subunits coded by each genetic system. Specific inhibitors of RNA transcription or protein translation with relative selectivity for each genetic system are indicated in blue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC149412&req=5

Figure 1: The mitochondrial electron transport chain complexes are encoded by two genetic systems: the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA). The mtDNA codes for 7 NADH dehydrogenase (ND) subunits for complex I, a cytochrome b for complex III, 3 cytochrome c oxidase (COX) subunits for complex IV, and 2 ATPase (ATPase6/8) for complex V. Complex II is solely encoded by nDNA. The solid arrows indicate the direction of electron flow in the respiration chain; dashed arrows indicate the flow of genetic information from mtDNA or nDNA to RNA to protein; the numbers indicate the actual number of protein subunits coded by each genetic system. Specific inhibitors of RNA transcription or protein translation with relative selectivity for each genetic system are indicated in blue.
Mentions: The most well-known and best-characterized function of mitochondria is the production of adenosine triphosphate (ATP) through oxidative phosphorylation. This process is accomplished by a series of protein complexes, collectively known as the respiratory chain, encoded by both nDNA and mtDNA. The complete respiratory chain contains at least 87 polypeptides, 13 of which are encoded by mtDNA. Hence, the majority of the respiratory chain components are nuclear-encoded and imported into mitochondria after their translation in the cytosol (Figure 1). Thus, oxidative phosphorylation is a unique biochemical process achieved by a well-coordinated effort of the protein products from two separate genomes (nuclear and mitochondrial) working in concert within the same cells. However, this process is not absolutely required to fulfill cellular energy requirements. Glycolysis can also generate ATP and provides a compensatory mechanism when oxidative phosphorylation becomes inefficient as a consequence of defects in the respiratory chain.

Bottom Line: Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis.Defects in mitochondrial function have long been suspected to contribute to the development and progression of cancer.In this review article, we aim to provide a brief summary of our current understanding of mitochondrial genetics and biology, review the mtDNA alterations reported in various types of cancer, and offer some perspective as to the emergence of mtDNA mutations, their functional consequences in cancer development, and therapeutic implications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. jcarew@mdanderson.org

ABSTRACT
Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Defects in mitochondrial function have long been suspected to contribute to the development and progression of cancer. In this review article, we aim to provide a brief summary of our current understanding of mitochondrial genetics and biology, review the mtDNA alterations reported in various types of cancer, and offer some perspective as to the emergence of mtDNA mutations, their functional consequences in cancer development, and therapeutic implications.

Show MeSH
Related in: MedlinePlus