Research ArticleCell Biology

Mitochondrial redox signaling enables repair of injured skeletal muscle cells

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Science Signaling  05 Sep 2017:
Vol. 10, Issue 495, eaaj1978
DOI: 10.1126/scisignal.aaj1978

Mitochondria for plasma membrane repair

Mechanical strain on cells can cause plasma membrane damage that must be repaired. Horn et al. found that mitochondria mediated a repair response in muscle cells (which experience mechanical strain during exercise) and nonmuscle cells. The influx of extracellular Ca2+ caused by plasma membrane injury triggered an increase in mitochondrial Ca2+ that initiated the generation of reactive oxygen species (ROS). Mitochondrially produced ROS activated actin polymerization and wound closure at the sites of plasma membrane injury. Quenching this source of ROS in mouse muscle exercised ex vivo resulted in greater damage to injured myofibers and reduced muscle force. These findings demonstrate that rampant quenching of ROS, such as with antioxidants (which are a popular nutritional supplement), may have detrimental effects that must be balanced with their potential benefits.


Strain and physical trauma to mechanically active cells, such as skeletal muscle myofibers, injures their plasma membranes, and mitochondrial function is required for their repair. We found that mitochondrial function was also needed for plasma membrane repair in myoblasts as well as nonmuscle cells, which depended on mitochondrial uptake of calcium through the mitochondrial calcium uniporter (MCU). Calcium uptake transiently increased the mitochondrial production of reactive oxygen species (ROS), which locally activated the guanosine triphosphatase (GTPase) RhoA, triggering F-actin accumulation at the site of injury and facilitating membrane repair. Blocking mitochondrial calcium uptake or ROS production prevented injury-triggered RhoA activation, actin polymerization, and plasma membrane repair. This repair mechanism was shared between myoblasts, nonmuscle cells, and mature skeletal myofibers. Quenching mitochondrial ROS in myofibers during eccentric exercise ex vivo caused increased damage to myofibers, resulting in a greater loss of muscle force. These results suggest a physiological role for mitochondria in plasma membrane repair in injured cells, a role that highlights a beneficial effect of ROS.

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