Mitochondria serve as vital powerhouses within cells, driving essential cellular functions through energy production. This energy generation occurs within the respiratory chain, comprised of five complexes known as CI through CV. While these complexes can assemble into supercomplexes, the mechanisms governing this process remain elusive. However, a recent study sheds light on the assembly mechanisms of these supercomplexes, revealing their critical role in cardiac regeneration. Spearheaded by Dr. José Antonio Enríquez at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Dr. Nadia Mercader from the University of Berne in Switzerland, this study investigates the impact of mitochondrial assembly factors on cardiac health.
Published in Developmental Cell, the study highlights a pivotal role played by a member of the Cox7a protein family in assembling CIV dimers, crucial for optimal mitochondrial function and energy production. This protein family comprises Cox7a1, Cox7a2, and Cox7a2l (also known as SCAF1). Previous research suggested that the inclusion of SCAF1 in CIV promotes its association with CIII, forming a respiratory supercomplex called the respirasome. Conversely, the absence of Cox7a1 inhibits CIV dimer formation, affecting mitochondrial function. Notably, the study employs zebrafish models, demonstrating that the loss of Cox7a1 impacts skeletal muscle, particularly affecting weight and swimming ability. Dr. Enríquez explains that Cox7a1 is predominantly expressed in striated muscle cells, affecting both skeletal and cardiac muscles.
Interestingly, while skeletal muscle is adversely affected by the absence of Cox7a1, cardiac muscle shows improved regenerative capabilities in response to injury. This suggests a crucial role for Cox7a1 in activating cardiac repair mechanisms post-injury. To delve deeper into Cox7a1's function, researchers conducted proteomic and metabolomic analyses on zebrafish lacking Cox7a1, revealing significant metabolic differences compared to unaffected fish. Dr. Mercader emphasizes the potential implications of these findings, indicating a link between mitochondrial supercomplex assembly and metabolic control, offering avenues for developing therapies for cardiac and metabolic disorders.
In summary, the study underscores the significant influence of mitochondrial assembly factors on metabolic regulation. This advancement in understanding cellular mechanisms involved in cardiac regeneration could pave the way for novel therapeutic approaches targeting cardiac and metabolic conditions.
