Cardiomyocyte prohibitin ablation reprograms cardiac metabolism revealing a pathogenic role for mTORC1 in dilated cardiomyopathy

Cardiomyocytes, the muscle cells of the heart, require a delicate balance between energy production and biosynthesis for proper function. A key player in this balance are prohibitins-1 and -2 (PHB1, 2), which form a ring-like complex in the cell's membranes and regulate growth, metabolism, and autophagy. Researchers have found that removing the PHB complex in adult mice leads to unchecked activity of a protein complex called mTORC1 and a shift in glucose metabolism, favoring the production of new amino acids.

This change is coupled with disruptions in mitochondrial function and impaired autophagy, resulting in severe enlargement of the heart and death within three months. Importantly, the researchers discovered that blocking mTORC1 activity could only prevent the pathological remodeling of the heart in female mice. These findings shed light on new ways that the PHB complex influences carbon flux and the development of heart disease.