Disruption of the homo-dimerization of the mitochondrial complex IV improves heart regeneration but negatively affects skeletal muscle mass
Presented by: Carolina García-Poyatos
Presentation time:
According to the plasticity model, the mitochondrial electron transport chain is a dynamic system in which monomeric respiratory complexes can be physically linked together in larger structures called super-complexes in order to optimize its function according to metabolic cell demands.
The homo and hetero super-assembly of CIV have been proposed to mediated by a family of proteins of complex IV, the Cox7a family which is composed by three members. Cox7a1 would mediate the homo dimerization of CIV, Cox7a2 would stabilize the monomer form and Cox7a2l mediates the super-assembly between complex III and complex IV (Cogliati et al. Nature 2016).
In this project we focused on the role of Cox7a1. Cox7a1 is highly expressed in skeletal and heart muscle. Moreover, it has been proposed as an embryonic-transition marker given that its expression starts right after mammals’ birth (West et al. Oncotarget 2017).
Using zebrafish and mouse genetic models we have probed its role in the homo-dimerization and homo-multimerization of complex IV. Zebrafish null allele models for cox7a1 resulted to have reduced skeletal muscle mass with consequences in their exercise capacity but, however, they also showed an improvement in their heart regeneration capacity.
Evidences suggest that the homo dimerization of complex IV mediated by Cox7a1 confers a metabolic maturation to the muscle tissue with negative consequences for the regenerative capacity of the heart but positive for proper muscle strength. This work present Cox7a1 as a possible target to improve the regenerative capacity of the heart.
The homo and hetero super-assembly of CIV have been proposed to mediated by a family of proteins of complex IV, the Cox7a family which is composed by three members. Cox7a1 would mediate the homo dimerization of CIV, Cox7a2 would stabilize the monomer form and Cox7a2l mediates the super-assembly between complex III and complex IV (Cogliati et al. Nature 2016).
In this project we focused on the role of Cox7a1. Cox7a1 is highly expressed in skeletal and heart muscle. Moreover, it has been proposed as an embryonic-transition marker given that its expression starts right after mammals’ birth (West et al. Oncotarget 2017).
Using zebrafish and mouse genetic models we have probed its role in the homo-dimerization and homo-multimerization of complex IV. Zebrafish null allele models for cox7a1 resulted to have reduced skeletal muscle mass with consequences in their exercise capacity but, however, they also showed an improvement in their heart regeneration capacity.
Evidences suggest that the homo dimerization of complex IV mediated by Cox7a1 confers a metabolic maturation to the muscle tissue with negative consequences for the regenerative capacity of the heart but positive for proper muscle strength. This work present Cox7a1 as a possible target to improve the regenerative capacity of the heart.