We analyzed which are the mechanisms driving the plasticity of heart muscle cells to re-enter cell division, a prerequisite of heart regeneration. We found that within mitochondria, the supramolecular organization of the respiratory chain dictates to some extent the regenerative capacity of cardiac muscle cells to respond to injury with entry into the cell cycle.
The findings are of interest as they provide a possible targeting route to transiently manipulate the ability of cardiac muscle cells to divide. This can in the future be exploited by the identification of small molecules inhibiting the specific respiratory complex assembly.
Cox7a1 controls skeletal muscle physiology and heart regeneration through complex IV dimerization.
García-Poyatos C, Arora P, Calvo E, Marques IJ, Kirschke N, Galardi-Castilla M, Lembke C, Meer M, Fernández-Montes P, Ernst A, Haberthür D, Hlushchuk R, Vázquez J, Vermathen P, Enríquez JA, Mercader N.Dev Cell. 2024 Jul 22;59(14):1824-1841.e10. doi: 10.1016/j.devcel.2024.04.012.
A second main finding from this ERC project comes from the study of the effect of a parental cardiac lesion on offspring. We were able to identify that in mice there is intergenerational inheritance of a neonatal cardiac lesion from one generation to the next. Pups from males with a cardiac cryolesion revealed alterations in cardiac function in the neonatal period and physiological alterations suggesting a better recovery after cardiac injury.
Our results, that need further validation in other models, suggests non-genetic inheritance of an experience across one generation in mammals.
Cox7a1 controls skeletal muscle physiology and heart regeneration through complex IV dimerization.
García-Poyatos C, Arora P, Calvo E, Marques IJ, Kirschke N, Galardi-Castilla M, Lembke C, Meer M, Fernández-Montes P, Ernst A, Haberthür D, Hlushchuk R, Vázquez J, Vermathen P, Enríquez JA, Mercader N.Dev Cell. 2024 Jul 22;59(14):1824-1841.e10. doi: 10.1016/j.devcel.2024.04.012.
