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Cited by 53Muscle Physiology and DisordersMitochondrial Function and PathologyAutophagy in Disease and Therapy

Molecular Signalling towards Mitochondrial Breakdown Is Enhanced in Skeletal Muscle of Patients with Chronic Obstructive Pulmonary Disease (COPD)

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Leermakers, P. A., Schols, A. M. W. J., Kneppers, A. E. M., Kelders, M. C. J. M., de Theije, C. C., Lainscak, M., Gosker, H. R.·2018·Scientific Reports
DOI 10.1038/s41598-018-33471-2PMC PMC6177478
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Abstract

Abstract Loss of skeletal muscle mitochondrial oxidative capacity is well-established in patients with COPD, but the role of mitochondrial breakdown herein is largely unexplored. Currently, we studied if mitochondrial breakdown signalling is increased in skeletal muscle of COPD patients and associates with the loss of mitochondrial content, and whether it is affected in patients with iron deficiency (ID) or systemic inflammation. Therefore, mitophagy, autophagy, mitochondrial dynamics and content markers were analysed in vastus lateralis biopsies of COPD patients (N = 95, FEV1% predicted: 39.0 [31.0–53.6]) and healthy controls (N = 15, FEV1% predicted: 112.8 [107.5–125.5]). Sub-analyses were performed on patients stratified by ID or C-reactive protein (CRP). Compared with controls, COPD patients had lower muscle mitochondrial content, higher BNIP3L and lower FUNDC1 protein, and higher Parkin protein and gene-expression. BNIP3L and Parkin protein levels inversely correlated with mtDNA/gDNA ratio and FEV1% predicted. ID-COPD patients had lower BNIP3L protein and higher BNIP3 gene-expression, while high CRP patients had higher BNIP3 and autophagy-related protein levels. In conclusion, our data indicates that mitochondrial breakdown signalling is increased in skeletal muscle of COPD patients, and is related to disease severity and loss of mitochondrial content. Moreover, systemic inflammation is associated with higher BNIP3 and autophagy-related protein levels.

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Cited by

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Authors
Leermakers, P. A., Schols, A. M. W. J., Kneppers, A. E. M., Kelders, M. C. J. M., de Theije, C. C., Lainscak, M., & Gosker, H. R.
Affiliations
Maastricht University Medical Centre (NL)
Corresponding author
Leermakers, P. A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-10-09
Volume
8
Issue
1
Pages
15007-15007
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-33471-2
PMC
PMC6177478
OpenAlex
W2895431767
Cited by
53
References
4
Citations by year
2026: 6 · 2025: 9 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 2
FWCI
1.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • NUTRIM Graduate Programme
  • Lung Foundation Netherlands
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
chronic obstructive pulmonary disease, skeletal muscle, mitophagy, autophagy, mitochondrial dynamics, BNIP3, FUNDC1, Parkin, iron deficiency, systemic inflammation, C-reactive protein, vastus lateralis, mitochondrial content, disease severity
MeSH terms
Aged, Autophagy, C-Reactive Protein, DNA, Mitochondrial, Female, Gene Expression Regulation, Humans, Inflammation, Male, Membrane Proteins, Middle Aged, Mitochondria, Proto-Oncogene Proteins, Signal Transduction, Muscle, Skeletal, Anemia, Iron-Deficiency, Mitochondrial Proteins, Tumor Suppressor Proteins, Pulmonary Disease, Chronic Obstructive, Ubiquitin-Protein Ligases, Mitophagy

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