Key result
Cardiomyocyte-restricted deletion of Crls1 prevented the postnatal rise in cristae density and respiratory proteins, causing heart failure and death by 2 weeks of age, whereas deletion of Tafazzin did not disrupt maturation.
Why the study?
Cardiolipin is essential for respiratory chain integrity, but its specific function in postnatal cardiac maturation and the roles of its synthesis versus remodeling were undefined.
Does cardiomyocyte-restricted deletion of Crls1 or Tafazzin affect mitochondrial maturation and survival in neonatal mice?
Does cardiomyocyte-restricted deletion of Crls1 or Tafazzin affect mitochondrial maturation and survival in neonatal mice?
De novo synthesis of cardiolipin, rather than its remodeling, is critical for the biogenesis of the respiratory chain and postnatal cardiac maturation.
Answers are grounded in this paper and cite their sources.
Crls1-dependent cardiolipin synthesis is required for neonatal cardiac maturation in mice; leaves open therapeutic targeting in human congenital heart disease.
Postnatal maturation of the mammalian heart requires a vast increase in respiratory enzymes. The mitochondria-specific lipid cardiolipin (CL) is essential for respiratory chain integrity but has no defined function in heart maturation. Here, we determined how the two steps of CL biogenesis, de novo synthesis and acyl chain remodeling, affect the maturation of cardiac mitochondria in mice. Cardiomyocyte-restricted deletion of the CL synthase Crls1 in late gestation does not affect CL levels at birth but blocks the increase in the tissue concentration of CL observed during normal postnatal maturation. Deletion of Crls1 prevents the postnatal rise in cristae density and in the intramitochondrial concentration of respiratory proteins. This inhibits cardiac development, precipitates heart failure, and causes death by the age of 2 weeks. In contrast, ablation of CL remodeling by cardiomyocyte-restricted deletion of Tafazzin does not disrupt mitochondrial maturation or cardiac development, although it has a similar effect on the CL concentration and profoundly alters the CL species composition. Our data show that CL synthesis, but not CL remodeling, controls expression of the respiratory chain by a mechanism independent of the CL concentration.
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Ren et al. (2026) studied Heart maturation and cardiomyopathy. Cardiomyocyte-restricted deletion of Crls1 vs. Littermate controls and TafazzinKO mice was evaluated on Survival and respiratory chain biogenesis. Cardiomyocyte-restricted deletion of Crls1 prevented the postnatal rise in cristae density and respiratory proteins, causing heart failure and death by 2 weeks of age, whereas deletion of Tafazzin did not disrupt maturation.
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