Proteomics

Dataset Information

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Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer


ABSTRACT: Complex I (CI) is the first enzyme of the mitochondrial respiratory chain and couples the electron transfer with proton pumping. Mutations in genes encoding CI subunits can frequently cause inborn metabolic errors. We applied proteome and metabolome profiling of patient-derived cells harboring pathogenic mutations in two distinct CI genes to elucidate underlying pathomechanisms on the molecular level. Our results indicated that the electron transfer within CI was interrupted in both patients by different mechanisms. We showed that the biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of CI and disrupted the electron transfer between two iron–sulfur clusters. Strikingly interesting and in contrast to the proteome, metabolome profiling illustrated that the pattern of dysregulated metabolites was almost identical in both patients, such as the inhibitory feedback on the TCA cycle and altered glutathione levels, indicative for reactive oxygen species (ROS) stress. Our findings deciphered pathological mechanisms of CI deficiency to better understand inborn metabolic errors.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Skin Fibroblast

DISEASE(S): Mitochondrial Complex I Deficiency

SUBMITTER: David Meierhofer  

LAB HEAD: David Meierhofer

PROVIDER: PXD009743 | Pride | 2019-10-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Ctrl_JH_repli1_1D.raw Raw
Ctrl_JH_repli1_SCX3.raw Raw
Ctrl_JH_repli1_SCX4.raw Raw
Ctrl_JH_repli1_SCX5.raw Raw
Ctrl_JH_repli1_SCXX.raw Raw
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Publications

Mutations in <i>NDUFS1</i> Cause Metabolic Reprogramming and Disruption of the Electron Transfer.

Ni Yang Y   Hagras Muhammad A MA   Konstantopoulou Vassiliki V   Mayr Johannes A JA   Stuchebrukhov Alexei A AA   Meierhofer David D  

Cells 20190925 10


Complex I (CI) is the first enzyme of the mitochondrial respiratory chain and couples the electron transfer with proton pumping. Mutations in genes encoding CI subunits can frequently cause inborn metabolic errors. We applied proteome and metabolome profiling of patient-derived cells harboring pathogenic mutations in two distinct CI genes to elucidate underlying pathomechanisms on the molecular level. Our results indicated that the electron transfer within CI was interrupted in both patients by  ...[more]

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