Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics.

Abstract

The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of 02 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 mlmin'1ml-1 with pyruvate/malate and 14.5 ml min'1-ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity ofeach of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals.In spite of the pivotal role of mitochondria in oxidative metabolism, their role in determining the oxygen flow through the respiratory system in mammals is still controversial. On the basis of evidence gained from human and animal training studies it is commonly held that mitochondrial oxidative capacity is vastly in excess of the capacity of the cardiovascular system to deliver oxygen (1). The currently most-accepted view is that the cardiovascular system limits maximal oxygen consumption (Vo2 max) during short-term heavy exercise (2) and that an increase in the quantity of mitochondria in muscle tissue with training is important mainly for an improved endurance capacity or fatigue resistance and for substrate selection (3,4).The results of comparative studies using allometric (5) and adaptive variation (6) of Vo2 ma. are in marked contrast to the studies that used exercise training to modify the maximal transport capacity of the respiratory system. The comparative approach demonstrated that among species with severalfold differences in weight-specific Vo2 ma there was a close correlation between Vo2 maxc and whole body mitochondrial content; consequently, the maximal in vivo oxygen consumption of mitochondria covered only a narrow range, 3-5 ml of

Regulation of oxidative phosphorylation through parallel activation

“…In intact human skeletal muscle the maximal VO 2 recalculated for the mitochondria volume is 2-5(-7) times greater than in isolated mitochondria [47] (see also [48][49][50] and calculations in [13]). It was postulated that the maximal VO 2 in heart [75] and in skeletal muscle in quadrupeds [76] matches well the maximal VO 2 in isolated heart mitochondia and skeletal muscle mitochondria, respectively; however, as it is discussed below, the interpretation of these results is not so strightforward.…”

“…It has been also postulated that in quadrupeds the whole animal maximal sustained oxygen uptake is similar, when recalculated for the mitochondria volume, to the maximal oxygen uptake in isolated mitochondria [76,91]. However, a detailed analysis of the experimental data presented in [76] and [91] demonstrates that this conclusion is not so straightforward [45].…”

“…However, a detailed analysis of the experimental data presented in [76] and [91] demonstrates that this conclusion is not so straightforward [45]. whole body exercise is at least twice greater than in isolated mitochondria.…”

Exercise-induced maximal metabolic rate scales with muscle aerobic capacity

“…It must be noted that the active mitochondrial surface, the inner mitochondrial membrane (Fig.·8), where oxidative phosphorylation takes place, shows invariant density in the mitochondria both with respect to body mass and aerobic capacity (Hoppeler and Lindstedt, 1985;Schwerzmann et al, 1989) so that the active surface is directly proportional to mitochondrial volume. We therefore conclude that MMR indeed scales with the surface area of inner mitochondrial membranes such that for each ml·O 2 consumed per minute at V O ∑ max the muscle contains 7·m 2 of active membrane.…”

Cardiac Basal Metabolism.

“…For reasons already enumerated, we believe that the mouse heart will use only about 1/3 as much energy per beat as the human heart, so there may be only a 4-fold difference in its total myocardial energy flux compared with man's (see Table 3a). It is clear that during maximal exercise some mammals (such as man and dog) can increase their myocardial energy flux more than 5-fold, and the values become near to the maximum oxidative phosphorylation capacity of their hearts [134,135]. We have estimated, on the basis of their mitochondrial volume fraction and the knowledge that 1 g of mitochondria consumes about 4 ml O 2 /min [6,135], that human hearts have an oxidative capacity in excess of 200 mW g Ϫ1 and would It is interesting to note that rodents have a very reduced exercise tolerance compared with man's [136].…”