Importance of mitochondrial P(O2) in maximal O2 transport and utilization: a theoretical analysis

Abstract

In previous calculations of how the O2 transport system limits .VO2(max), it was reasonably assumed that mitochondrial P(O2) (Pm(O2)) could be neglected (set to zero). However, in reality, Pm(O2) must exceed zero and the red cell to mitochondrion diffusion gradient may therefore be reduced, impairing diffusive transport of O2 and .VO2(max). Accordingly, we investigated the influence of Pm(O2) on these calculations by coupling previously used equations for O2 transport to one for mitochondrial respiration relating mitochondrial .VO2 to P(O2). This hyperbolic function, characterized by its P50 and V˙MAX, allowed Pm(O2) to become a model output (rather than set to zero as previously). Simulations using data from exercising normal subjects showed that at .VO2(max), Pm(O2) was usually <1mmHg, and that the effects on .VO2(max) were minimal. However, when O2 transport capacity exceeded mitochondrial V˙MAX, or if P50 were elevated,Pm(O2) often reached double digit values, thereby reducing the diffusion gradient and significantly decreasing .VO2(max).

Keywords: Bioenergetics; Mitochondrial; Mitochondrial respiration; Oxygen transport.

Figure 1

Graphical analysis of diffusive transport of O₂ from muscle capillary to the mitochondria (dashed line) and subsequent utilization of O₂ through oxidative phosphorylation (solid line). See text for details.

Figure 2

Schematic representation of the oxygen transport and utilization system considered in this study and the five associated mass conservation equations governing O₂ transport (equations a–d) and utilization (equation e).

Figure 3

Graphical depiction of the hyperbolic equation for oxidative phosphorylation fitted to the data of Scandurra & Gnaiger (Scandurra and Gnaiger, 2010). p16. fig 3B).

Figure 4

Effects of considering mitochondrial respiration on maximal V̇_O2 and mitochondrial P_O2. For each V̇_MAX value, the four hyperbolic curves represent P₅₀ values of 0.1, 0.3, 0.5 and 1.0 mm Hg, left to right. See text for details.

Figure 5

Mitochondrial P_O2 (upper panel) and muscle O₂ diffusing capacity (lower panel) required to maintain V̇_O2 constant at the measured value across the domain of V̇_MAX and P₅₀ values at each altitude studied (see text for details).

Figure 6

Graphical depiction of the concept that even when the capacity for O₂ delivery exceeds O₂ utilization (upper panel) a change in O₂ delivery will change actual V̇_O2. Conversely, when the capacity for O₂ utilization exceeds O₂ delivery (lower panel) a change in O₂ utilization (increase in P₅₀ in this example) will change actual V̇_O2. Open circles: maximal O₂ delivery to mitochondria if Pm_O2 was zero. Closed circles: actual V̇_O2. Solid and dashed lines: as in Figure 1.

Figure 7

Estimation of mitochondrial P₅₀. Upper panel: least squares best fit (solid lines) to data (solid circles) for five trial P₅₀ values. Lower panel: closeness of fit to data reflected by the Root Mean Square error, showing that a P₅₀ of 0.30 mm Hg provides the best estimate.