Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle

Andreas Mæchel Fritzen; Frank B Thøgersen; Kasper Thybo; Christoffer Rasmus Vissing; Thomas O Krag; Cristina Ruiz-Ruiz; Lotte Risom; Flemming Wibrand; Louise Dalgas Høeg; Bente Kiens; Morten Duno; John Vissing; Tina Dysgaard Jeppesen

doi:10.3390/cells8030237

Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle

Andreas Mæchel Fritzen, Frank B Thøgersen, Kasper Thybo, Christoffer Rasmus Vissing, Thomas O Krag, Cristina Ruiz-Ruiz, Lotte Risom, Flemming Wibrand, Louise Dalgas Høeg, Bente Kiens, Morten Duno, John Vissing, Tina Dysgaard Jeppesen

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Abstract

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I⁻IV activities were increased by 51% and 46⁻61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I⁻IV activities by 29⁻36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.

Original language	English
Article number	237
Journal	Cells
Volume	8
Issue number	3
Number of pages	16
ISSN	2073-4409
DOIs	https://doi.org/10.3390/cells8030237
Publication status	Published - Mar 2019

Keywords

Faculty of Science
mtDNA
Mitochondria
Skeletal muscle
Exercise training
Mitochondrial biogenesis

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Fritzen et al_Cells_2019_Vol 8(3)_e237Final published version, 1.33 MBLicence: CC BY

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Fritzen, A. M., Thøgersen, F. B., Thybo, K., Vissing, C. R., Krag, T. O., Ruiz-Ruiz, C., Risom, L., Wibrand, F., Høeg, L. D., Kiens, B., Duno, M., Vissing, J., & Jeppesen, T. D. (2019). Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle. Cells, 8(3), Article 237. https://doi.org/10.3390/cells8030237

Fritzen, AM, Thøgersen, FB, Thybo, K, Vissing, CR, Krag, TO, Ruiz-Ruiz, C, Risom, L, Wibrand, F, Høeg, LD, Kiens, B, Duno, M, Vissing, J & Jeppesen, TD 2019, 'Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle', Cells, vol. 8, no. 3, 237. https://doi.org/10.3390/cells8030237

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title = "Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle",

abstract = "Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I⁻IV activities were increased by 51% and 46⁻61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I⁻IV activities by 29⁻36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.",

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AU - Fritzen, Andreas Mæchel

AU - Thøgersen, Frank B

AU - Thybo, Kasper

AU - Vissing, Christoffer Rasmus

AU - Krag, Thomas O

AU - Ruiz-Ruiz, Cristina

AU - Risom, Lotte

AU - Wibrand, Flemming

AU - Høeg, Louise Dalgas

AU - Kiens, Bente

AU - Duno, Morten

AU - Vissing, John

AU - Jeppesen, Tina Dysgaard

N1 - CURIS 2019 NEXS 095

PY - 2019/3

Y1 - 2019/3

N2 - Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I⁻IV activities were increased by 51% and 46⁻61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I⁻IV activities by 29⁻36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.

AB - Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I⁻IV activities were increased by 51% and 46⁻61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I⁻IV activities by 29⁻36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.

KW - Faculty of Science

KW - mtDNA

KW - Mitochondria

KW - Skeletal muscle

KW - Exercise training

KW - Mitochondrial biogenesis

U2 - 10.3390/cells8030237

DO - 10.3390/cells8030237

M3 - Journal article

C2 - 30871120

SN - 2073-4409

VL - 8

JO - Cells

JF - Cells

IS - 3

M1 - 237

ER -

Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle

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