Control of cell respiration by nitric oxide in Ataxia Telangiectasia lymphoblastoid cells.
Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative-nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the reversible inhibition of complex IV. The mitochondrial response to NO of AT lymphoblastoid cells was investigated. Cells isolated from three patients and three intrafamilial healthy controls were selected showing within each group a normal diploid karyotype and homogeneous telomere length. Different complex IV NO-inhibition patterns were induced by varying the electron flux through the respiratory chain, using exogenous cell membrane permeable electron donors. Under conditions of high electron flux the mitochondrial NO inhibition of respiration was greater in AT than in control cells (P< or =0.05). This property appears peculiar to AT, and correlates well to the higher concentration of cytochrome c detected in the AT cells. This finding is discussed on the basis of the proposed mechanism of reaction of NO with complex IV. It is suggested that the peculiar response of AT mitochondria to NO stress may be relevant to the mitochondrial metabolism of AT patients.
Department of Biochemical Sciences, Sapienza University of Roma, Roma, Italy.
Alessandra
A
Masci
Daniela
D
Mastronicola
Marzia
M
Arese
Maria
M
Piane
Andrea
A
De Amicis
Thomas J J
TJ
Blanck
Luciana
L
Chessa
Paolo
P
Sarti
D000255:Adenosine Triphosphate / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000378:metabolism*; D019069:Cell Respiration; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000502:physiology; D006019:Glycolysis; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010085:Oxidative Phosphorylation
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV