Twenty‐eight days of exposure to 3454 m increases mitochondrial volume density in human skeletal muscle

Abstract

Key pointsr It is generally accepted that mitochondrial volume density in human skeletal muscle diminishes with chronic high altitude exposure.r All data supporting this concept were collected during mountaineering expeditions, which are associated with the confounding effects of whole body negative energy balance.r Here we examine the effect of 28 days of exposure to 3454 m on skeletal muscle mitochondrial volume density in a setting where whole body weight, whole body composition, leg lean mass, skeletal muscle fibre area and maximal power output were preserved.r Our results demonstrate that total skeletal muscle mitochondrial volume density increases in response to high altitude exposure secondary to a preferential increase in intermyofibrillar mitochondrial populations.r This study provides direct evidence contradicting the notion that high altitude exposure diminishes skeletal muscle mitochondrial volume density, highlighting an inconsistent understanding of the role of hypoxia on skeletal muscle mitochondria.Abstract The role of hypoxia on skeletal muscle mitochondria is controversial. Studies superimposing exercise training on hypoxic exposure demonstrate an increase in skeletal muscle mitochondrial volume density (Mito VD ) over equivalent normoxic training. In contrast, reductions in both skeletal muscle mass and Mito VD have been reported following mountaineering expeditions. These observations may, however, be confounded by negative energy balance, which may obscure the results. Accordingly we sought to examine the effects of high altitude hypoxic exposure on mitochondrial characteristics, with emphasis on Mito VD , while minimizing changes in energy balance. For this purpose, skeletal muscle biopsies were obtained from nine lowlanders at sea level (Pre) and following 7 and 28 days of exposure to 3454 m. Maximal ergometer power output, whole body weight and composition, leg lean mass and skeletal muscle fibre area all remained unchanged following the altitude exposure. Transmission electron microscopy determined that intermyofibrillar (IMF) Mito VD was augmented (P = 0.028) by 11.5 ± 9.2% from Pre (5.05 ± 0.9%) to 28 Days (5.61 ± 0.04%). In contrast, there was no change in subsarcolemmal (SS) Mito VD . As a result, total Mito VD (IMF + SS) was increased (P = 0.031) from 6.20 ± 1.5% at Pre to 6.62 ± 1.4% at 28 Days (7.8 ± 9.3%). At the same time no changes in mass-specific respiratory capacities, mitochondrial protein or antioxidant content were found. This study demonstrates that skeletal muscle Mito VD may increase with 28 days acclimation to 3454 m.

Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis

“…This is in contrast to what we found for subjects exposed to hypoxia during a 28‐day sojourn at 3454 m [Ref. ]: in that study, we reported an increase in the intermyofibrillar population of mitochondria, whereas the subsarcolemmal population was unaffected by the hypoxic condition.…”

Evolved changes in the intracellular distribution and physiology of muscle mitochondria in high‐altitude native deer mice

“…In a more recent study when neutral energy balance was maintained, mitochondrial volume density in the muscle was shown to increase with prolonged exposure of lowland humans to high altitude (Jacobs et al . ). Comparable data in non‐human mammals are quite limited, but studies in lowland rodents have often suggested that hypoxia acclimation has relatively little effect on the oxidative capacity of muscle (León‐Velarde et al .…”

CrossTalk opposing view: Exercise training volume is more important than training intensity to promote increases in mitochondrial content

“…is the activity of citrate synthase (CS), an enzyme exclusively located in the mitochondria (Tonkonogi & Sahlin, 1997). While the validity of this biomarker to assess changes in mitochondrial content has been questioned (Jacobs et al 2016;Meinild Lundby et al 2018; pooled correlation between training-induced changes in CS activity and Mito VD was found to be r = 0.246, P > 0.05), it continues to be the most common marker used in exercise training studies.…”