The random collision model and a critical assessment of diffusion and collision in mitochondrial electron transport

Abstract

This review focuses on our studies over the past ten years which reveal that the mitochondrial inner membrane is a fluid-state rather than a solid-state membrane and that all membrane proteins and redox components which catalyze electron transport and ATP synthesis are in constant and independent diffusional motion. The studies reviewed represent the experimental basis for the random collision model of electron transport. We present five fundamental postulates upon which the random collision model of mitochondrial electron transport is founded: All redox components are independent lateral diffusants; Cytochrome c diffuses primarily in three dimensions; Electron transport is a diffusion-coupled kinetic process; Electron transport is a multicollisional, obstructed, long-range diffusional process; The rates of diffusion of the redox components have a direct influence on the overall kinetic process of electron transport and can be rate limiting, as in diffusion control. The experimental rationales and the results obtained in testing each of the five postulates of the random collision model are presented. In addition, we offer the basic concepts, criteria and experimental strategies that we believe are essential in considering the significance of the relationship between diffusion and electron transport. Finally, we critically explore and assess other contemporary studies on the diffusion of inner membrane components related to electron transport including studies on: rotational diffusion, immobile fractions, complex formation, dynamic aggregates, and rates of diffusion. Review of all available data confirms the random collision model and no data appear to exist that contravene it. It is concluded that mitochondrial electron transport is a diffusion-based random collision process and that diffusion has an integral and controlling affect on electron transport.

Supramolecular organizations in the aerobic respiratory chain of Escherichia coli

“…NADH: ferricyanide oxidoreductase activity was determined following oxidation of NADH at 340 nm (3 NADH ¼ 6.22 mM À1 cm À1 ) in a reaction buffer containing 100 mM MOPS pH 7.2, 250 mM NADH and 250 mM K 3 [Fe(CN) 6 ] [40]. Succinate:DCPIP oxidoreductase activity was monitored by following the PMS-coupled reduction of DCPIP at 578 nm at 37 C (3 DCPIP ¼ 20.5 mM À1 cm À1 ).…”

“…The resolved gradient was divided in 1 mL fractions (F1eF9 from highest to lowest molecular mass, respectively) and the respiratory chain activities with artificial electron acceptors, the oxygen consumption rates and heme b content were determined. NADH:K 3 [Fe(CN) 6 ] oxidoreductase activity was present throughout the gradient fractions being maximal in fraction 1. Such distribution may be explained by the presence of type I and II NADH:quinone oxidoreductases as monomers, homodimers or combined with other respiratory chain complexes in supercomplexes.…”

“…Supramolecular organization of respiratory chains has been recently extensively reported for all life domains, challenging the random diffusion model [6] and providing new evidence in strong support of the "solid state" model proposed by Chance and Williams [7]. In eukaryotes, supercomplexes formed by complexes I, III and IV, the so-called respirasomes, have been observed in mitochondria of bovine heart [8e10], mouse liver [11], potato tuber [12,13], Neurospora crassa [14] and Yarrowia lipolytica [15].…”

Questioning the functional relevance of mitochondrial supercomplexes by time-resolved analysis of the respiratory chain

“…Extensive studies by Hackenbrock and colleagues of the diffusion properties of the different actors of the respiratory chain, in particular of cytochrome c, brought compelling evidences for a random collision model (reviewed in ref. 8). Rich reviewed these issues and listed four different models ranging from "liquid" to "solid" state, the intermediate cases comprising the partial association of the individual components, or "patches" containing higher concentration of one or more cofactors (9).…”

Significance of Respirasomes for the Assembly/Stability of Human Respiratory Chain Complex I

“…1). Another major reason was the pioneering work of Hackenbrock and co-workers (2,3) who demonstrated that the concentration of free-diffusing components in the inner mitochondrial membrane and the collision rate between them is enough to explain the observed respiratory rates in mitochondria.…”