Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma

John Ogunbileje, Craig Porter, David Herndon, Tony Chao, Doaa R. Abdelrahman, Anastasia Papadimitriou, Maria Chondronikola, Teresa A. Zimmers, Paul T. Reidy, Blake Rasmussen, Labros S. Sidossis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria. In skeletal muscle of burn patients, concurrent activation of mTORC1 signaling and elevation in the fractional synthetic rate paralleled increased levels of proteasomes and elevated fractional breakdown rate. Burn patients had greater levels of oxidative stress markers as well as higher expression of mtUPR-related genes and proteins, suggesting that burns increased mitochondrial stress and protein damage. Indeed, upregulation of cytoprotective genes suggests hypermetabolism-induced oxidative stress postburn. In parallel to mtUPR activation postburn, mitochondrial- specific proteases (LONP1 and CLPP) and mitochondrial translocases (TIM23, TIM17B, and TOM40) were upregulated, suggesting increased mitochondrial protein degradation and transport of preprotein, respectively. Our data demonstrate that proteolysis occurs in both the cytosolic and mitochondrial compartments of skeletal muscle in severely burned patients. Increased mitochondrial protein turnover may be associated with increased protein damage due to hypermetabolism- induced oxidative stress and activation of mtUPR. Our results suggest a novel role for the mitochondria in burn-induced cachexia.

Original languageEnglish (US)
Pages (from-to)E436-E448
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016

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Skeletal Muscle
Mitochondrial Proteins
Wounds and Injuries
Oxidative Stress
Burns
Proteolysis
Cachexia
Heat-Shock Proteins
Mitochondria
Mitochondrial Turnover
Muscles
Body Surface Area
Protein Transport
Proteasome Endopeptidase Complex
Oxygen Consumption
Young Adult
Proteins
Peptide Hydrolases
Up-Regulation
Genes

Keywords

  • Burn injury
  • Cachexia
  • Hypermetabolism-induced oxidative stress
  • Mitochondria proteases
  • Mitochondrial unfolded protein response

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Medicine(all)
  • Physiology (medical)

Cite this

Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma. / Ogunbileje, John; Porter, Craig; Herndon, David; Chao, Tony; Abdelrahman, Doaa R.; Papadimitriou, Anastasia; Chondronikola, Maria; Zimmers, Teresa A.; Reidy, Paul T.; Rasmussen, Blake; Sidossis, Labros S.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 311, No. 2, 01.08.2016, p. E436-E448.

Research output: Contribution to journalArticle

Ogunbileje, J, Porter, C, Herndon, D, Chao, T, Abdelrahman, DR, Papadimitriou, A, Chondronikola, M, Zimmers, TA, Reidy, PT, Rasmussen, B & Sidossis, LS 2016, 'Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma', American Journal of Physiology - Endocrinology and Metabolism, vol. 311, no. 2, pp. E436-E448. https://doi.org/10.1152/ajpendo.00535.2015
Ogunbileje, John ; Porter, Craig ; Herndon, David ; Chao, Tony ; Abdelrahman, Doaa R. ; Papadimitriou, Anastasia ; Chondronikola, Maria ; Zimmers, Teresa A. ; Reidy, Paul T. ; Rasmussen, Blake ; Sidossis, Labros S. / Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 311, No. 2. pp. E436-E448.
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