Supercomplex Assembly Determines Electron Flux in the Mitochondrial Electron Transport Chain

TLDR

Mitochondrial respiratory complexes were traditionally viewed as freely diffusing units linked by mobile carriers, but recent proposals suggest that most complexes form supercomplexes such as the respirasome, raising questions about their functional significance and existence. The study aims to demonstrate that interactions between complexes I–III and III–IV create distinct CoQ and cytochrome‑c pools and that supercomplex assembly dynamically directs electron flow to maximize substrate utilization. The authors genetically disrupted the interfaces between complexes I–III and III–IV to assess how these interactions influence supercomplex formation and electron transport.

Abstract

The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respirasome (complexes I, III, and IV), complexes I and III, and complexes III and IV. The role of SCs is unclear, and their existence is debated. By genetic modulation of interactions between complexes I and III and III and IV, we show that these associations define dedicated CoQ and cyt c pools and that SC assembly is dynamic and organizes electron flux to optimize the use of available substrates.