Proteins in the sarcomere complex are stochastically removed and degraded and are replaced by newly translated proteins. Sarcomere turnover occurs at a similar rate within cardiomyocytes and across the heart and slows with ageing. These findings, published in Circulation Research, contrast with the prevailing ‘protein pool’ model of sarcomere turnover, in which sarcomeres were thought to be maintained by free recycling of proteins between the sarcomere and cytoplasmic pools of soluble proteins.

To investigate the mechanisms of sarcomere proteostasis, Izhak Kehat and colleagues developed a pulse–chase approach based on the irreversible covalent binding of differently coloured fluorescent HaloTag ligands to image the replacement of older sarcomeric proteins (labelled in green) by newly translated ones (labelled in far-red) in cardiomyocytes in culture and in vivo.