Clarifying the cardiac proteasome paradox: protein quality control.

Correct folding of proteins is crucial for proper protein, cell, and organ function.1 Mutations and cellular stresses, some of which occur during pathology, can lead to incorrect folding and subsequent loss of protein function. If it goes uncorrected, then this loss of protein function, along with the toxicity associated with the accumulation of misfolded proteins in cells, results in eventual organ failure.2 Many diseases, including neurodegenerative, hepatic, endocrine, and cardiovascular disorders, are thought to be associated with, if not caused by, the organ failure resulting from the accumulation of misfolded proteins.3 For example, in the heart, accumulation of misfolded proteins has been associated with hypertrophic and dilated cardiomyopathies as well as ischemic heart disease.4