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SHR Neuro Cancer Cardio Lipid Metab Microb

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 PUBMED Central FullText FullText_MUG

 

Co-authors Med Uni Graz
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)
Apolipoproteins - genetics, metabolism
Cardiolipins - metabolism
Electron Transport - genetics
Gene Deletion - administration & dosage
Humans - administration & dosage
Membrane Proteins - metabolism
Mitochondria - metabolism
Mitochondrial Membranes - metabolism
Mitochondrial Proteins - genetics
Protein Binding - genetics
Protein Subunits - genetics
Transferases (Other Substituted Phosphate Groups) - metabolism

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