<i>S</i> ‐Glutathionylation of troponin I (fast) increases contractile apparatus Ca ²⁺ sensitivity in fast‐twitch muscle fibres of rats and humans

Abstract

Key points Reactive oxygen‐based molecules generated within muscle fibres in both exercise and pathological conditions can greatly affect muscle function. These and consequent reactions can lead to either decreased or increased force response by the contractile proteins, but the mechanisms are unknown. This study demonstrates that the increase in force response appears to be due to a specific chemical process, known as S‐ glutathionylation, of a particular cysteine residue present on the troponin I molecule in fast‐twitch muscle fibres, which is involved in sensing and responding to changes in intracellular calcium levels. S ‐Glutathionylation can occur when glutathione, the primary cellular anti‐oxidant, reacts with oxidized cysteine residues. S ‐Glutathionylation of troponin I not only helps protect the molecule from oxidative stress, but evidently also makes the contractile apparatus much more sensitive to calcium ions. This process seemingly occurs in exercising humans and is likely to be an important mechanism helping delay onset of muscle fatigue.