Extracellular acidosis at pH 6.5 induces ubiquitin-dependent degradation of MIC60 in rat cardiomyocytes, resulting in disruption of mitochondrial cristae structure, reduced ATP production, and impaired cardiac function, and restoration of MIC60 levels reverses these effects.

When the fluid around heart cells becomes too acidic, it causes a key mitochondrial protein called MIC60 to be tagged with ubiquitin molecules, which marks it for destruction by the cell's protein-recycling system. Without MIC60, the internal folds of the mitochondria collapse, preventing efficient energy production. This leads to less ATP, damaged heart cells, and weaker heart pumping. Adding back MIC60 restores the mitochondrial structure and energy output, fixing the heart's function.