Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Research output: Contribution to journalJournal articleResearchpeer-review

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Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia. / Groennebaek, Thomas; Billeskov, Tine Borum; Schytz, Camilla Tvede; Jespersen, Nichlas Riise; Bøtker, Hans Erik; Olsen, Rikke Kathrine Jentoft; Eldrup, Nikolaj; Nielsen, Joachim; Farup, Jean; De Paoli, Frank Vincenzo; Vissing, Kristian.

In: Cells, Vol. 9, No. 3, 570, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Groennebaek, T, Billeskov, TB, Schytz, CT, Jespersen, NR, Bøtker, HE, Olsen, RKJ, Eldrup, N, Nielsen, J, Farup, J, De Paoli, FV & Vissing, K 2020, 'Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia', Cells, vol. 9, no. 3, 570. https://doi.org/10.3390/cells9030570

APA

Groennebaek, T., Billeskov, T. B., Schytz, C. T., Jespersen, N. R., Bøtker, H. E., Olsen, R. K. J., Eldrup, N., Nielsen, J., Farup, J., De Paoli, F. V., & Vissing, K. (2020). Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia. Cells, 9(3), [570]. https://doi.org/10.3390/cells9030570

Vancouver

Groennebaek T, Billeskov TB, Schytz CT, Jespersen NR, Bøtker HE, Olsen RKJ et al. Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia. Cells. 2020;9(3). 570. https://doi.org/10.3390/cells9030570

Author

Groennebaek, Thomas ; Billeskov, Tine Borum ; Schytz, Camilla Tvede ; Jespersen, Nichlas Riise ; Bøtker, Hans Erik ; Olsen, Rikke Kathrine Jentoft ; Eldrup, Nikolaj ; Nielsen, Joachim ; Farup, Jean ; De Paoli, Frank Vincenzo ; Vissing, Kristian. / Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia. In: Cells. 2020 ; Vol. 9, No. 3.

Bibtex

@article{8faa985e03cf45b6b2b2450cc1e221ec,
title = "Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia",
abstract = "Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.",
keywords = "Aged, Biomarkers/metabolism, Cell Respiration, Extremities/blood supply, Female, Humans, Ischemia/complications, Male, Mitochondria, Muscle/metabolism, Mitochondrial Dynamics, Mitochondrial Proteins/metabolism, Muscular Diseases/complications",
author = "Thomas Groennebaek and Billeskov, {Tine Borum} and Schytz, {Camilla Tvede} and Jespersen, {Nichlas Riise} and B{\o}tker, {Hans Erik} and Olsen, {Rikke Kathrine Jentoft} and Nikolaj Eldrup and Joachim Nielsen and Jean Farup and {De Paoli}, {Frank Vincenzo} and Kristian Vissing",
year = "2020",
doi = "10.3390/cells9030570",
language = "English",
volume = "9",
journal = "Cells",
issn = "2073-4409",
publisher = "MDPI AG",
number = "3",

}

RIS

TY - JOUR

T1 - Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

AU - Groennebaek, Thomas

AU - Billeskov, Tine Borum

AU - Schytz, Camilla Tvede

AU - Jespersen, Nichlas Riise

AU - Bøtker, Hans Erik

AU - Olsen, Rikke Kathrine Jentoft

AU - Eldrup, Nikolaj

AU - Nielsen, Joachim

AU - Farup, Jean

AU - De Paoli, Frank Vincenzo

AU - Vissing, Kristian

PY - 2020

Y1 - 2020

N2 - Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.

AB - Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.

KW - Aged

KW - Biomarkers/metabolism

KW - Cell Respiration

KW - Extremities/blood supply

KW - Female

KW - Humans

KW - Ischemia/complications

KW - Male

KW - Mitochondria, Muscle/metabolism

KW - Mitochondrial Dynamics

KW - Mitochondrial Proteins/metabolism

KW - Muscular Diseases/complications

U2 - 10.3390/cells9030570

DO - 10.3390/cells9030570

M3 - Journal article

C2 - 32121096

VL - 9

JO - Cells

JF - Cells

SN - 2073-4409

IS - 3

M1 - 570

ER -

ID: 262916388