Evidence for mitochondrial respiratory deficiency in rat rhabdomyosarcoma cells.
BACKGROUND
Mitochondria 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.


RESULTS
Mitochondrial 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.


CONCLUSIONS
A 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.
Jahnke
Vanessa E
VE
Université de Lyon, Université Jean Monnet, Laboratoire de Physiologie de l'Exercice EA4338, Saint Etienne, France.
Sabido
Odile
O
Defour
Aurélia
A
Castells
Josiane
J
Lefai
Etienne
E
Roussel
Damien
D
Freyssenet
Damien
D
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004579:Electron Transport; D006861:Hydrogen Peroxide / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology
D006861:Hydrogen Peroxide