Mitochondrial OXPHOS Functions in R1H Rhabdomyosarcoma and Skeletal Muscles of the Rat

Kuhnt, Thomas; Pelz, Tanja; Qu, Xiao-ying; Hänsgen, Gabriele; Dunst, Jürgen; Gellerich, Frank N.

doi:10.1007/s11064-006-9254-0

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…Importantly, of the mitochondrial respiratory chain complexes, complex I was the most severely impaired [34]. Together with the observation that complex I activity is reduced in R1H cells [35], our report that cardiolipin content is strongly decreased in R1H cells may thus contribute to explain the decrease in the respiratory capacity of R1H cells. Overall, these data suggest that a tight regulation between protein and phospholipid syntheses is necessary to produce functional mitochondria.…”

Section: Discussionsupporting

confidence: 66%

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells

et al. 2010

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BackgroundMitochondria can sense signals linked to variations in energy demand to regulate nuclear gene expression. This retrograde signaling pathway is presumed to be involved in the regulation of myoblast proliferation and differentiation. Rhabdomyosarcoma cells are characterized by their failure to both irreversibly exit the cell cycle and complete myogenic differentiation. However, it is currently unknown whether mitochondria are involved in the failure of rhabdomyosarcoma cells to differentiate.Methodology/Principal FindingsMitochondrial biogenesis and metabolism were studied in rat L6E9 myoblasts and R1H rhabdomyosacoma cells during the cell cycle and after 36 hours of differentiation. Using a combination of flow cytometry, polarographic and molecular analyses, we evidenced a marked decrease in the cardiolipin content of R1H cells cultured in growth and differentiation media, together with a significant increase in the content of mitochondrial biogenesis factors and mitochondrial respiratory chain proteins. Altogether, these data indicate that the mitochondrial inner membrane composition and the overall process of mitochondrial biogenesis are markedly altered in R1H cells. Importantly, the dysregulation of protein-to-cardiolipin ratio was associated with major deficiencies in both basal and maximal mitochondrial respiration rates. This deficiency in mitochondrial respiration probably contributes to the inability of R1H cells to decrease mitochondrial H2O2 level at the onset of differentiation.Conclusion/SignificanceA defect in the regulation of mitochondrial biogenesis and mitochondrial metabolism may thus be an epigenetic mechanism that may contribute to the tumoral behavior of R1H cells. Our data underline the importance of mitochondria in the regulation of myogenic differentiation.

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Section: Discussionsupporting

confidence: 66%

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells

et al. 2010

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“…Other reasons for that might be related to specific impairments of mitochondria. In cancer cells, the mitochondria are characterized by defective respiratory chain complexes I and III and decreased β-F 1 -ATPase [ 279 – 291 ], and the type of mitochondrial impairment appears to determine the clinical phenotype [ 279 , 290 ]. Accordingly, benign oncocytomas are characterized by impaired complex I, but enhanced expression of other respiratory chain complexes and matrix enzymes, together with upregulation of mitochondrial tissue content, the latter changes likely compensating the insufficient complex I.…”

Section: Involvement Of Mitochondria In Pathological Processes and DImentioning

confidence: 99%

Mitochondria and Energetic Depression in Cell Pathophysiology

Seppet

Gruno

Peetsalu

et al. 2009

IJMS

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Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting OPEN ACCESSInt. J. Mol. Sci. 2009, 10 2253 from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell's ability to do work and control the intracellular Ca 2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis.

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“…More specific, functional abnormalities of the respiratory chain complexes were found, in contrast to muscle cells. In R1H a decrease of complex I-activity and a varied ratio of pyruvate-dependent succinate respiration in favor of succinate respiration were verified 57 .…”

Section: Bioenergetic Properties and Metabolic Vulnerabilitiesmentioning

confidence: 87%

“…This deficiency in mitochondrial respiration probably contributes to the inability of R1H cells to decrease mitochondrial H 2 O 2 level at the onset of differentiation 56 . Further, it is showed that in R1H not only the amount of mitochondria was decreased, but also those tumor mitochondria present specific functional properties 57 . More specific, functional abnormalities of the respiratory chain complexes were found, in contrast to muscle cells.…”

Section: Bioenergetic Properties and Metabolic Vulnerabilitiesmentioning

confidence: 97%

Signaling pathways that overactivate metabolism and drive neoplasia, in rhabdomyosarcoma

Tselios¹,

Lambrou²

2019

JRPMS

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Inflammatory pathways that affect NF-kB, STAT3 and AP-1 are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, and in turn regulate expression of cytokines, adhesion molecules, proteases, anti-apoptotic factors, DNA repair factors, cell cycle and cell metabolism factors. NF-kB, STAT3 and AP-1 thereby control cell transformation, cell survival, proliferation, invasion, angiogenesis, metastasis, chemoresistance, and radioresistance of cancer. Deregulated activation of NF-kB, STAT3 and AP-1 family proteins is often associated with transition of cells from a differentiated phenotype to a stem cell-like unit, which may abnormally retain features of the differentiated cell. Common theme is the presence of features that are essential for the preservation of cell functions under unfavorable conditions related to stress,

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Mitochondrial OXPHOS Functions in R1H Rhabdomyosarcoma and Skeletal Muscles of the Rat

Cited by 5 publications

References 41 publications

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells

Mitochondria and Energetic Depression in Cell Pathophysiology

Signaling pathways that overactivate metabolism and drive neoplasia, in rhabdomyosarcoma

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