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Carew, Jennifer S.; Huang, Peng

doi:10.1186/1476-4598-1-9

Cited by 509 publications

(157 citation statements)

References 77 publications

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“…Broadly, these can originate from either enhancing signals that directly increase glycolysis or from inhibiting energy metabolism by the mitochondria, rendering glycolysis the major source of ATP. Glycolytic enzymes are induced by oncogenes (Dang and Semenza, 1999;Plas and Thompson, 2005) or by the hypoxia-inducible transcription factor (HIF) (Maxwell, 2005a), whereas oxidative phosphorylation can be inhibited by mutations in mitochondrial DNA (Carew and Huang, 2002;Modica-Napolitano and Singh, 2004) or a dysfunctional TCA cycle owing to loss of function of mitochondrial tumour suppressor genes (Eng et al, 2003;Gottlieb and Tomlinson, 2005). This review focuses on a newly discovered biochemical link between the loss of mitochondrial tumour suppressors and the induction of glycolysis by the HIF pathway.…”

Section: Enhanced Glycolysis In Cancer Cellsmentioning

confidence: 99%

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

2006

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The phenomenon of enhanced glycolysis in tumours has been acknowledged for decades, but biochemical evidence to explain it is only just beginning to emerge. A significant hint as to the triggers and advantages of enhanced glycolysis in tumours was supplied by the recent discovery that succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tumour suppressors and which associated, for the first time, mitochondrial enzymes and their dysfunction with tumorigenesis. Further steps forward showed that the substrates of SDH and FH, succinate and fumarate, respectively, can mediate a 'metabolic signalling' pathway. Succinate or fumarate, which accumulate in mitochondria owing to the inactivation of SDH or FH, leak out to the cytosol, where they inhibit a family of prolyl hydroxylase enzymes (PHDs). Depending on the PHD inhibited, two newly recognized pathways that support tumour maintenance may ensue: affected cells become resistant to certain apoptotic signals and/or activate a pseudohypoxic response that enhances glycolysis and is conveyed by hypoxia-inducible factor.

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Section: Enhanced Glycolysis In Cancer Cellsmentioning

confidence: 99%

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

2006

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“…59 In mice, a defect in the proofreading function of the mitochondrial DNA polymerase POLG (D257A) results in somatic accumulation of mutations in the mitochondrial genome and a progressive decline in mitochondrial function. These mice develop a progeroid phenotype with early onset of several age-related diseases and premature death of mice by the age of 15 mo.…”

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confidence: 99%

Mitophagy in hematopoietic stem cells

Joshi

Kundu

2013

Autophagy

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“…Within cells, there are thousands of mitochondria, each containing multiple copies of mtDNA. mtDNA mutations are random, increase with age (5,6), and are thought to occur because of the presence of free-radicalgenerating enzymes, potentiated by poor DNA repair mechanisms and the lack of protective histones (7,8). These mutations can affect all copies of the mitochondrial genome (homoplasmy) or a proportion thereof (heteroplasmy).…”

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confidence: 99%

Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission

Greaves

Preston

Tadrous

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

272

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The understanding of the fixation of mutations within human tissues and their subsequent clonal expansion is a considerable problem, of which little is known. We have previously shown that nononcogenic mutations in the mitochondrial genome occur in one of a number of morphologically normal colonic crypt stem cells, the progeny of which later occupy the whole crypt. We propose that these wholly mutated crypts then clonally expand by crypt fission, where each crypt divides into two mutated daughter crypts. Here we show that (i) mutated crypts in the process of fission share the same mutated mitochondrial genotype not present in neighboring cytochrome c oxidase-positive crypts (the odds of this being a random event are >2.48 ؋ 10 9 :1); (ii) neighboring mutated crypts have the same genotype, which is different from adjacent cytochrome c oxidase-positive crypts; (iii) mutated crypts are clustered together throughout the colon; and (iv) patches of cytochrome c oxidase-deficient crypts increase in size with age. We thus demonstrate definitively that crypt fission is the mechanism by which mutations spread in the normal human colon. This has important implications for the biology of the normal adult human colon and possibly for the growth and spread of colorectal neoplasms.fission ͉ mitochondria

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Untitled

Cited by 509 publications

References 77 publications

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer

Mitophagy in hematopoietic stem cells

Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission

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