Cardiolipin Remodeling in Cardiovascular Diseases: Implication for Mitochondrial Dysfunction

Aim

Mitochondrial dysfunction is pivotal in both the development and progression of cardiovascular diseases (CVDs), though its exact mechanisms remain unclear. Cardiolipin (CL), a key mitochondrial phospholipid, is involved in various mitochondrial functions, including dynamics, membrane integrity, oxidative phosphorylation, mitochondrial DNA maintenance, and mitophagy. Due to enzyme limitations in the CL biosynthesis pathway, premature CL undergoes remodeling to acquire the proper acyl content for its function. Disruption in CL composition leads to mitochondrial dysfunction, contributing significantly to CVDs. The purpose of this review is to explore the role of CL remodeling in the mechanism of mitochondrial dysfunction that occurs in CVDs.

Methods

This review examines CL’s critical role in mitochondrial function, the consequences of CL deficiencies in CVDs, and the impact of mutations or deficiencies in CL remodeling enzymes-tafazzin (TAZ), Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1), and Monolysocardiolipin acyltransferase (MLCLAT1)-on CL homeostasis, mitochondrial function, and CVDs pathogenesis. Emerging CL-targeted therapies are also reviewed.

Results

Proper CL function is crucial for mitochondrial health and cardioprotection. Pathological CL remodeling due to mutations or deficiencies in TAZ, ALCAT1, or MLCLAT1, drives mitochondrial dysfunction and accelerates CVDs progression. Based on these insights, current CL-based therapeutic strategies are also summarized, including precision medicine/gene therapy, targeted pharmacotherapy, and dietary interventions.

Conclusion

Targeting CL may represent a promising clinical therapeutic strategy for CVDs.