In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 3, No. 10 ( 2020-10), p. e202000711-
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 F 1 F o –ATP synthase complex and integration of F 1 subunits into the monomeric F 1 F o –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.
Type of Medium:
Online Resource
ISSN:
2575-1077
DOI:
10.26508/lsa.202000711
Language:
English
Publisher:
Life Science Alliance, LLC
Publication Date:
2020
detail.hit.zdb_id:
2948687-7
