Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching

Autor: Bumsoo Ahn, Rojina Ranjit, Pavithra Premkumar, Gavin Pharaoh, Katarzyna M. Piekarz, Satoshi Matsuzaki, Dennis R. Claflin, Kaitlyn Riddle, Jennifer Judge, Shylesh Bhaskaran, Kavithalakshmi Satara Natarajan, Erika Barboza, Benjamin Wronowski, Michael Kinter, Kenneth M. Humphries, Timothy M. Griffin, Willard M. Freeman, Arlan Richardson, Susan V. Brooks, Holly Van Remmen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 10, Iss 2, Pp 411-428 (2019)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12375
Popis: Abstract Background Excess reactive oxygen species (ROS) and muscle weakness occur in parallel in multiple pathological conditions. However, the causative role of skeletal muscle mitochondrial ROS (mtROS) on neuromuscular junction (NMJ) morphology and function and muscle weakness has not been directly investigated. Methods We generated mice lacking skeletal muscle‐specific manganese‐superoxide dismutase (mSod2KO) to increase mtROS using a cre‐Lox approach driven by human skeletal actin. We determined primary functional parameters of skeletal muscle mitochondrial function (respiration, ROS, and calcium retention capacity) using permeabilized muscle fibres and isolated muscle mitochondria. We assessed contractile properties of isolated skeletal muscle using in situ and in vitro preparations and whole lumbrical muscles to elucidate the mechanisms of contractile dysfunction. Results The mSod2KO mice, contrary to our prediction, exhibit a 10–15% increase in muscle mass associated with an ~50% increase in central nuclei and ~35% increase in branched fibres (P
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