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Conference Papers Year : 2022

Coordination between mitochondrial-associated membranes MAMs, mitochondrial function and protein synthesis in exercised and myopathic muscles

Tuifua L,
  • Function : Author
Laurence Pessemesse
  • Function : Author
  • PersonId : 1079744
Barbara Vernus
Asikan E
  • Function : Author
Guillaume Py
  • Function : Author
  • PersonId : 1136804
Béatrice Chabi

Abstract

Skeletal muscles mitochondria are key organelles that control not only ATP production but also fulfill important short term and/or long-term metabolic adaptations to various stimuli and constraints including exercise. However, mitochondria do not function independently of the cell context, as they form dynamic and privileged contact sites with the endoplasmic reticulum (ER), called mitochondrial-associated membranes (MAMs). MAMs play important roles in calcium transfer as well as phospholipids synthesis, exchange and transfer between ER and mitochondria and in the control of glucose metabolism. Recent reports, including our own publications indicate that MAMs stand as a crucial hub in skeletal muscles that integrate and coordinate ATP production by mitochondria and protein synthesis, a major energy-consuming process. This important checkpoint allows to respond to energetic challenging conditions like exercise, fasting or hypoxia by blunting Akt/mTOR dependent protein synthesis, which spares ATP and limits energetic stress [1]. Moreover, we have also shown recently that a single bout of physical exercise can induce an immediate decrease of MAMs contacts sites in skeletal muscles and a simultaneous reduction of protein synthesis [2]. Neuromuscular myopathies are often associated with mitochondrial defects that can affect various functions or content of this organelle, and have important impact in the phenotype of these pathologies. Moreover, alterations in the muscle protein balance (synthesis versus degradation) are frequently observed in neuromuscular dystrophies, sometimes associated with MAMs dysfunction. However, we do not know yet whether MAMs defects could be a cause or a consequence in these muscular pathologies as MAMs dynamics remains poorly characterized in skeletal muscles in relation with mitochondrial function and protein synthesis notably following exercise. In this study, we first analyzed the coordination between protein synthesis and mitochondrial respiration as a first step to describe the functional relationship of the hub made of MAMs dynamics, mitochondrial respiration and protein synthesis in skeletal muscle. Therefore, mitochondrial respiration and protein synthesis as well as AMPK and AKT/mTOR signaling were compared in skeletal muscle homogenates from 6 months old (mo) C57BL/6J at rest, following acute exercise (45 min treadmill exercise) and after a recovery period (3 h). These analyses were also performed in skeletal muscle homogenates of 12 mo control (C57BL/10) and mdx mice, model of Duchenne Muscular Dystrophy (DMD). Preliminary results showed no significant change in mitochondrial respiration while AMPK activation is rapidly induced following acute exercise and goes back to rest level during recovery period. In contrast, protein synthesis tended to be blunted following acute exercise and during the recovery period. Data from mdx mice are currently under investigation. This study will shed light on the functional relationship between mitochondrial respiration, protein synthesis and MAMs dynamics in resting, exercised and pathologic skeletal muscles. This could pave the way for future therapeutic routes to treat muscular disorders.
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Dates and versions

hal-04233589 , version 1 (09-10-2023)

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  • HAL Id : hal-04233589 , version 1

Cite

Colomb Marie, Tuifua L,, Christelle Bertrand-Gaday, Laurence Pessemesse, Barbara Vernus, et al.. Coordination between mitochondrial-associated membranes MAMs, mitochondrial function and protein synthesis in exercised and myopathic muscles. Bioblast 2022: BEC Inaugural Conference, Jun 2022, Obergurgl, Australia. ⟨hal-04233589⟩
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