QUATERNARY AND QUINARY ORGANIZATION OF RESPIRATORY COMPLEX SUBUNITS TO ADAPT PROTEOSTASIS-STRESS

Phase separation and reversible aggregation of proteins is a well-recognized adaptive strategy to survive stress. Here, we show that RCC subunits are engaged into improved super-quaternary organizations inside mitochondria during proteostasis stress. Assembly and oligomeric organizations of Complex II and V are consolidated while Complex I, III and IV are increasingly incorporated into respiratory supercomplexes in multiple cell-lines with different proteostasis and metabolic demands. Further, our results suggest that improved supra-organization of respiratory complexes (iSRC) is an outcome of conformational optimization towards better enzyme activity and co-terminus to appearance of aggregates of RCC subunits in stressed cells. Simultaneous reversion of iSRC and disappearance of the aggregates during stress-withdrawal indicates complementarity between these quaternary and quinary proteome-reorganization mechanisms. iSRC appears to be the pre-emptive and deterministic ensemble over stochastic aggregation as it offers direct fitness-benefit.