Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

Joachim Nielsen; Kasper D Gejl; Martin Hey-Mogensen; Hans-Christer Holmberg; Charlotte Suetta; Peter Krustrup; Coen P H Elemans; Niels Ørtenblad

doi:10.1113/jp273040

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

Joachim Nielsen, Kasper D Gejl, Martin Hey-Mogensen, Hans-Christer Holmberg, Charlotte Suetta, Peter Krustrup, Coen P H Elemans, Niels Ørtenblad

Department of Clinical Medicine

65 Citations (Scopus)

Abstract

KEY POINTS: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.

ABSTRACT: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.

Original language	English
Journal	The Journal of Physiology
Volume	595
Issue number	9
Pages (from-to)	2839-2847
Number of pages	9
ISSN	0022-3751
DOIs	https://doi.org/10.1113/jp273040
Publication status	Published - 1 May 2017

Keywords

Adult
Animals
Energy Metabolism
Exercise
Female
Finches
Humans
Male
Middle Aged
Mitochondria, Muscle/metabolism
Muscle, Skeletal/metabolism
Oxygen Consumption

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title = "Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle",

abstract = "KEY POINTS: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.ABSTRACT: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.",

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author = "Joachim Nielsen and Gejl, {Kasper D} and Martin Hey-Mogensen and Hans-Christer Holmberg and Charlotte Suetta and Peter Krustrup and Elemans, {Coen P H} and Niels {\O}rtenblad",

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year = "2017",

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T1 - Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

AU - Nielsen, Joachim

AU - Gejl, Kasper D

AU - Hey-Mogensen, Martin

AU - Holmberg, Hans-Christer

AU - Suetta, Charlotte

AU - Krustrup, Peter

AU - Elemans, Coen P H

AU - Ørtenblad, Niels

PY - 2017/5/1

Y1 - 2017/5/1

N2 - KEY POINTS: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.ABSTRACT: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.

AB - KEY POINTS: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.ABSTRACT: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.

KW - Adult

KW - Animals

KW - Energy Metabolism

KW - Exercise

KW - Female

KW - Finches

KW - Humans

KW - Male

KW - Middle Aged

KW - Mitochondria, Muscle/metabolism

KW - Muscle, Skeletal/metabolism

KW - Oxygen Consumption

U2 - 10.1113/jp273040

DO - 10.1113/jp273040

M3 - Journal article

C2 - 27696420

SN - 0022-3751

VL - 595

SP - 2839

EP - 2847

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 9

ER -

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

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Keywords

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