Dozens of MICOS-interacting proteins with diverse functions have been described, and the astonishingly broad spectrum of diseases linked to mutations impacting on MICOS or MICOS partners point to additional tissue-specific functions that go far beyond CJ formation.
To dissect the role of the individual MICOS subunits, we disrupted the genes of the seven MICOS proteins (MIC10, MIC13, MIC19, MIC25, MIC26, MIC27, and MIC60) in HeLa cells utilizing CRISPR/Cas9 genome editing (for details on the experimental strategy, see Appendix Table S1).
Since the MICOS complex is highly conserved in form and function throughout evolution, we will highlight the importance of MICOS for mammals.
The MICOS complex regulates the formation of CJs and mediates the contact between the OMM and IMM by interacting with the SAM (the sorting and assembly machinery) complex, which is located on the...
MICOS deficiency leads to a grossly altered inner membrane architecture resulting in far-reaching functional perturbations in mitochondria. Consequently, mutations affecting the function of MICOS are responsible for a diverse spectrum of human diseases.
Aspects of mitochondrial regulation under physiological and pathological conditions are outlined, in particular the role of dysregulated MICOS protein subunit Mic60 in Parkinson’s disease, the relations between mitochondrial quality control and proteins, and mitochondria as signaling organelles.
The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is ...
Overall, we propose that the MICOS complex integrates numerous spatial and temporal cues to regulate the dynamic microenvironment, along with IM architecture, which are involved in multiple pathways controlling mitochondrial biogenesis.