Skeletal muscle unloading results in increased mitophagy and decreased mitochondrial biogenesis regulation

Pieter A. Leermakers*, Anita E. M. Kneppers, Annemie M. W. J. Schols, Marco C. J. M. Kelders, Chiel C. de Theije, Lex B. Verdijk, Luc J. C. van Loon, Ramon C. J. Langen, Harry R. Gosker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

IntroductionPhysical inactivity significantly contributes to loss of muscle mass and performance in bed-bound patients. Loss of skeletal muscle mitochondrial content has been well-established in muscle unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading-induced loss of muscle mitochondrial content is preceded by increased mitophagy- and decreased mitochondrial biogenesis-signaling during the early stages of unloading.

MethodsWe analyzed a comprehensive set of molecular markers involved in mitochondrial-autophagy, -biogenesis, -dynamics, and -content, in the gastrocnemius muscle of C57BL/6J mice subjected to 0- and 3-days hind limb suspension, and in biopsies from human vastus lateralis muscle obtained before and after 7days of one-leg immobilization.

ResultsIn both mice and men, short-term skeletal muscle unloading results in molecular marker patterns indicative of increased receptor-mediated mitophagy and decreased mitochondrial biogenesis regulation, before apparent loss of mitochondrial content.

DiscussionThese results emphasize the early-onset of skeletal muscle disuse-induced mitochondrial remodeling.

Original languageEnglish
Pages (from-to)769-778
Number of pages10
JournalMuscle & Nerve
Volume60
Issue number6
Early online date23 Oct 2019
DOIs
Publication statusPublished - Dec 2019

Keywords

  • inactivity
  • mitochondria
  • mitochondrial biogenesis
  • mitophagy
  • muscle unloading
  • skeletal muscle
  • LEG IMMOBILIZATION
  • OVER-EXPRESSION
  • SOLEUS MUSCLE
  • DYNAMICS
  • ATROPHY
  • FUNDC1
  • ACTIVATION
  • PATHWAYS
  • GENES
  • YOUNG

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