Difference between revisions of "Mayr 2004 Pediatr Res"
| Line 5: | Line 5: | ||
|year=2004 | |year=2004 | ||
|journal=Pediatr Res | |journal=Pediatr Res | ||
|abstract=The FoF1-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory | |abstract=The FoF1-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory Complex I and compensatory increase in the content of Complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ''ATP6'' and ''ATP8'' genes indicates a nuclear origin of the defect. | ||
|mipnetlab=CZ_Prague_Houstek J, CZ Prague Bioenergetics | |mipnetlab=CZ_Prague_Houstek J, CZ Prague Bioenergetics | ||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Respiration, nDNA;cell genetics, mt-Medicine, Patients | ||
|organism=Human | |organism=Human | ||
|tissues=Heart, Skeletal muscle | |tissues=Heart, Skeletal muscle | ||
|model cell lines=Fibroblast | |model cell lines=Fibroblast | ||
|preparations=Permeabilized tissue | |preparations=Permeabilized tissue | ||
|enzymes=Complex I, Complex III, Complex IV; Cytochrome c Oxidase, Complex V; ATP Synthase | |||
|enzymes=Complex V; ATP Synthase | |diseases=Other | ||
|couplingstates=LEAK, OXPHOS | |||
|substratestates=CII | |||
|instruments=Oxygraph-2k | |||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
Revision as of 10:37, 12 August 2013
| Mayr JA, Paul J, Pecina P, Kurnik P, Forster H, Fotschl U, Sperl W, Houstek J (2004) Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase. Pediatr Res 55: 988-994. |
Mayr JA, Paul J, Pecina P, Kurnik P, Forster H, Fotschl U, Sperl W, Houstek J (2004) Pediatr Res
Abstract: The FoF1-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory Complex I and compensatory increase in the content of Complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect.
• O2k-Network Lab: CZ_Prague_Houstek J, CZ Prague Bioenergetics
Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine, Patients
Pathology: Other
Organism: Human Tissue;cell: Heart, Skeletal muscle Preparation: Permeabilized tissue Enzyme: Complex I, Complex III, Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Complex V; ATP Synthase"Complex V; ATP Synthase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.
Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k
