Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "Kiss 2013 FASEB J"

From Bioblast
Line 9: Line 9:
}}
}}
{{Labeling
{{Labeling
|instruments=Oxygraph-2k
|area=Respiration, Genetic knockout;overexpression
|injuries=Mitochondrial Disease; Degenerative Disease and Defect, Genetic Defect; Knockdown; Overexpression
|organism=Mouse
|organism=Mouse
|enzymes=TCA Cycle and Matrix Dehydrogenases
|diseases=Neurodegenerative
|topics=ADP, ATP, Ion&substrate transport
|couplingstates=OXPHOS
|couplingstates=OXPHOS
|enzymes=TCA Cycle and Matrix Dehydrogenases
|substratestates=CI
|topics=ATP; ADP; AMP; PCr
|instruments=Oxygraph-2k
}}
}}

Revision as of 09:25, 12 August 2013

Publications in the MiPMap
Kiss G, Konrad C, Doczi J, Starkov AA, Kawamata H, Manfredi G, Zhang SF, Gibson GE, Beal MF, Adam-Vizi V, Chinopoulos C (2013) The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. FASEB J [Epub ahead of print].

Β» PMID: 23475850

Kiss G, Konrad C, Doczi J, Starkov AA, Kawamata H, Manfredi G, Zhang SF, Gibson GE, Beal MF, Adam-Vizi V, Chinopoulos C (2013) FASEB J

Abstract: A decline in α-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by substrate-level phosphorylation catalyzed by succinyl-CoA ligase. Here, we demonstrate ATP consumption in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice with a deficiency of either dihydrolipoyl succinyltransferase (DLST) or dihydrolipoyl dehydrogenase (DLD) that exhibit a 20-48% decrease in KGDHC activity. Import of ATP into the mitochondrial matrix of transgenic mice was attributed to a shift in the reversal potential of the adenine nucleotide translocase toward more negative values due to diminished matrix substrate-level phosphorylation, which causes the translocase to reverse prematurely. Immunoreactivity of all three subunits of succinyl-CoA ligase and maximal enzymatic activity were unaffected in transgenic mice as compared to wild-type littermates. Therefore, decreased matrix substrate-level phosphorylation was due to diminished provision of succinyl-CoA. These results were corroborated further by the finding that mitochondria from wild-type mice respiring on substrates supporting substrate-level phosphorylation exhibited ∼30% higher ADP-ATP exchange rates compared to those obtained from DLST+/- or DLD+/- littermates. We propose that KGDHC-associated pathologies are a consequence of the inability of respiration-impaired mitochondria to rely on "in-house" mitochondrial ATP reserves.


β€’ O2k-Network Lab: HU Budapest Chinopoulos C


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Neurodegenerative 

Organism: Mouse 


Enzyme: TCA Cycle and Matrix Dehydrogenases"TCA Cycle and Matrix Dehydrogenases" 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.  Regulation: ADP, ATP, Ion&substrate transport"Ion&substrate transport" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.  Coupling state: OXPHOS 

HRR: Oxygraph-2k