Fig. 6.

Proposed mechanism of UnDOx to control in-register aggregation of distal I-band titin. Several Ig domains from the distal I-band titin region (mainly the NH₂-terminal half) are suggested to be in a partially unfolded state in vivo. S-glutathionylation of the unfolded domains stabilizes the unfolded state, which promotes aggregation of parallel titin molecules. Stretch under oxidant stress conditions recruits more Ig domains to the unfolded state and further promotes this mechanism. The result is an improved anchorage of the titin spring under mechanical and oxidant stress.