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Cancer
Cardio
Lipid
Metab
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Anand, R; Kondadi, AK; Meisterknecht, J; Golombek, M; Nortmann, O; Riedel, J; Peifer-Weiß, L; Brocke-Ahmadinejad, N; Schlütermann, D; Stork, B; Eichmann, TO; Wittig, I; Reichert, AS.
MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes.
Life Sci Alliance. 2020; 3(10):
Doi: 10.26508/lsa.202000711
[OPEN ACCESS]
Web of Science
PubMed
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FullText_MUG
- Co-authors Med Uni Graz
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Eichmann Thomas
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- Abstract:
- Homologous apolipoproteins of MICOS complex, MIC26 and MIC27, show an antagonistic regulation of their protein levels, making it difficult to deduce their individual functions using a single gene deletion. We obtained single and double knockout (DKO) human cells of MIC26 and MIC27 and found that DKO show more concentric onion-like cristae with loss of CJs than any single deletion indicating overlapping roles in formation of CJs. Using a combination of complexome profiling, STED nanoscopy, and blue-native gel electrophoresis, we found that MIC26 and MIC27 are dispensable for the stability and integration of the remaining MICOS subunits into the complex suggesting that they assemble late into the MICOS complex. MIC26 and MIC27 are cooperatively required for the integrity of respiratory chain (super) complexes (RCs/SC) and the F1Fo-ATP synthase complex and integration of F1 subunits into the monomeric F1Fo-ATP synthase. While cardiolipin was reduced in DKO cells, overexpression of cardiolipin synthase in DKO restores the stability of RCs/SC. Overall, we propose that MIC26 and MIC27 are cooperatively required for global integrity and stability of multimeric OXPHOS complexes by modulating cardiolipin levels.
- Find related publications in this database (using NLM MeSH Indexing)
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Apolipoproteins - genetics, metabolism
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Cardiolipins - metabolism
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Electron Transport - genetics
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Gene Deletion - administration & dosage
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Humans - administration & dosage
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Membrane Proteins - metabolism
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Mitochondria - metabolism
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Mitochondrial Membranes - metabolism
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Mitochondrial Proteins - genetics
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Protein Binding - genetics
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Protein Subunits - genetics
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Transferases (Other Substituted Phosphate Groups) - metabolism