Defects in mitochondrial metabolism and cancer

Gaude, Edoardo; Frezza, Christian

doi:10.1186/2049-3002-2-10

Cited by 214 publications

(182 citation statements)

References 89 publications

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“…It is tempting to speculate that a variable intracellular localization of Foxg1 in these different conditions may contribute to explain these apparently contradictory findings. An amount of recent evidence suggests that metabolism and mitochondrial functions play a critical role in cancer development and progression (32). The identification of the multiple localization of Foxg1 (nucleus, cytosol, and mitochondrial matrix) opens the way to study the mechanisms exploited by this protein to tie together gene expression, metabolism, and mitochondrial bioenergetics.…”

Section: Discussionmentioning

confidence: 99%

Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

Pancrazi

Benedetto

Colombaioni

et al. 2015

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

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Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show that a fraction of Foxg1 is localized within the mitochondria in cell lines, primary neuronal or glial cell cultures, and in the mouse cortex. Import of Foxg1 in isolated mitochondria appears to be membrane potential-dependent. Amino acids (aa) 277-302 were identified as critical for mitochondrial localization. Overexpression of full-length Foxg1 enhanced mitochondrial membrane potential (ΔΨm) and promoted mitochondrial fission and mitosis. Conversely, overexpression of the C-term Foxg1 (aa 272-481), which is selectively localized in the mitochondrial matrix, enhanced organelle fusion and promoted the early phase of neuronal differentiation. These findings suggest that the different subcellular localizations of Foxg1 control the machinery that brings about cell differentiation, replication, and bioenergetics, possibly linking mitochondrial functions to embryonic development and pathological conditions.Rett syndrome | autism | cancer | brain cortex | development

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Section: Discussionmentioning

confidence: 99%

Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

Pancrazi

Benedetto

Colombaioni

et al. 2015

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

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“…SDHB is one of the subunits of SDH takes parts in TCA [5], ATP is an indicator of energy metabolism. We found that the level ATP was decreased in SDHB-silenced cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…SDHB is one of the subunits of SDH which takes part in TCA cycle and respiratory chain [5], AMPK could modulate metabolic stresses such as hypoxia. Study showed mitochondrial dysfunctions could result in reduced HIF-1α protein synthesis through AMPK-dependent manner in HepG2 cells [37].…”

Section: Discussionmentioning

confidence: 99%

“…Succinate dehydrogenase (SDH), known as succinateubiquinone oxidoreductase, is a mitochondrial enzyme complex that catalyses the oxidation of succinate to fumarate in the citric acid cycle and participates in the electron transport chain [5]. Mutations of the SDH gene determine the genetic basis of paragangliomas/pheochromocytomas (PCCs/PGLs) [6,7] and associated tumour syndromes (Carney-Stratakis syndrome and Carney triad) [8].…”

Section: Introductionmentioning

confidence: 99%

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Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1¿ pathway in human ovarian cancer in vitro

Chen

Liu

Zhang

et al. 2014

Journal of Ovarian Research

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Background: Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Numerous evidences demonstrate that cancer cells undergo metabolic abnormality during tumorigenesis in tumor microenvironment and further facilitate tumor progression. Succinate dehydrogenase (SDH or Complex II) is one of the important enzymes in the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been recognized as a tumor suppressor. However the role of SDHB in ovarian cancer is still unclear. Methods: Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer was investigated in vitro, using proliferation, migration and invasion assays. To explore the mechanism, proliferation and migration related proteins such as Bcl-2, cleaved caspase 3, p-ERK, MMP-2, and p-FAK were examined by western blot. P-P38, p-AMPKα, and HIF-1α were also examined by western blot. CoCl2 was used to induce HIF-1α expression in SKOV3 and A2780 cells.

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“…There has been an accumulation of evidences suggesting that the mitochondria plays a key role in cancer (reviewed in Chatterjee et al, 2006;Gaude and Frezza, 2014). Mutations to mitochondrial DNA may lead to mitochondrial dysfunction and the metabolic reprogramming of cancer cells leading to the modulation in cellular processes involved in the initiation and progression of cancer.…”

Section: Introductionmentioning

confidence: 99%

Novel Mutations in Cholangiocarcinoma with Low Frequencies Revealed by Whole Mitochondrial Genome Sequencing

Muisuk

Silsirivanit²,

Imtawil³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

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Defects in mitochondrial metabolism and cancer

Cited by 214 publications

References 89 publications

Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1¿ pathway in human ovarian cancer in vitro

Novel Mutations in Cholangiocarcinoma with Low Frequencies Revealed by Whole Mitochondrial Genome Sequencing

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