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. 2021 Aug 16;131(16):e149415. doi: 10.1172/JCI149415

Figure 3. Sarcomere protein quality control requires BAG3.

Figure 3

In the normal heart, the BAG3-hsp70-hspB8 complex localizes to the Z-disc, where it provides chaperone-assisted selective autophagy for sarcomere proteins, which helps to maintain normal contractile function. However, in heart failure (specifically heart failure with reduced ejection fraction, HFrEF), sarcomere-localized BAG3 levels drop, and thus ubiquitinated proteins are not removed and instead stay imbedded in the sarcomere lattice structure. These nuclear, stress-misfolded proteins contribute to the cellular contractile dysfunction observed in heart failure.