Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD)

P. A. Leermakers*, A. M. W. J. Schols, A. E. M. Kneppers, M. C. J. M. Kelders, C. C. de Theije, M. Lainscak, H. R. Gosker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number15007
Number of pages13
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 9 Oct 2018

Keywords

  • RECEPTOR-MEDIATED MITOPHAGY
  • CHRONIC HEART-FAILURE
  • LOCOMOTOR MUSCLE
  • MAMMALIAN-CELLS
  • DYSFUNCTION
  • AUTOPHAGY
  • PROTEIN
  • FUNDC1
  • REHABILITATION
  • METABOLISM

Fingerprint

Dive into the research topics of 'Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD)'. Together they form a unique fingerprint.

Cite this