The hearts of two mice, one which is normal and one in which the gene for Ptpmt1 has been removed, leading to heart failure. Image credit: Zheng, Li, Li et al. (CC BY 4.0).
Cells are powered by mitochondria, a group of organelles that produce chemical energy in the form of molecules called ATP. This energy is derived from the breakdown of carbohydrates, fats, and proteins.
The number of mitochondria in a cell and the energy source they use to produce ATP varies depending on the type of cell. Mitochondria can also switch the molecules they use to produce energy when the cell is responding to stress or disease.
The heart and the skeletal muscles – which allow movement – are two tissues that require large amounts of energy, but it remained unknown whether disrupting mitochondrial fuel selection affects how these tissues work.
To answer these questions, Zheng, Li, Li et al. investigated the role of an enzyme found in mitochondria called Ptpmt1. Genetically deleting Ptpmt1 in the heart and skeletal muscle of mice showed that while the development of these organs was not affected, mitochondria in these cells switched from using carbohydrates to using fats as an energy source. Over time, this shift damaged both the mitochondria and the tissues, leading to muscle wasting, heart failure, and sudden death in the mice. This suggests that balanced use of carbohydrates and fats is essential for the muscles and heart.
These findings imply that long-term use of medications that alter the fuel that mitochondria use may be detrimental to patients’ health and could cause heart dysfunction. This may be important for future drug development, as well as informing decisions about medication taken in the clinic.
