The article discusses the role of mitochondrial lipids in regulating bioenergetic flux, particularly through oxidative phosphorylation (OXPHOS). Mitochondrial membranes contain a unique lipid composition, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), which are essential for OXPHOS and other mitochondrial functions. The lipid composition affects lipid-to-protein interactions, membrane properties, and cristae ultrastructure, all of which influence mitochondrial bioenergetics. The review highlights the biosynthesis pathways of these lipids and their roles in physiology, human diseases, and the regulation of mitochondrial bioenergetics. Genetic diseases associated with mutations in genes involved in mitochondrial lipid biosynthesis, such as Barth syndrome and Sengers syndrome, are discussed, along with non-communicable conditions like exercise-induced changes in mitochondrial lipid composition and their implications in metabolic diseases. The article also explores the influence of cell type on mitochondrial membrane lipid composition and the dynamic role of mitochondrial lipids in regulating bioenergetics, including ATP production, proton uncoupling, and mitochondrial electron leak. Finally, the authors propose a "bagpipe hypothesis" to explain the dynamic regulation of cristae architecture and bioenergetics by mitochondrial lipids.The article discusses the role of mitochondrial lipids in regulating bioenergetic flux, particularly through oxidative phosphorylation (OXPHOS). Mitochondrial membranes contain a unique lipid composition, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), which are essential for OXPHOS and other mitochondrial functions. The lipid composition affects lipid-to-protein interactions, membrane properties, and cristae ultrastructure, all of which influence mitochondrial bioenergetics. The review highlights the biosynthesis pathways of these lipids and their roles in physiology, human diseases, and the regulation of mitochondrial bioenergetics. Genetic diseases associated with mutations in genes involved in mitochondrial lipid biosynthesis, such as Barth syndrome and Sengers syndrome, are discussed, along with non-communicable conditions like exercise-induced changes in mitochondrial lipid composition and their implications in metabolic diseases. The article also explores the influence of cell type on mitochondrial membrane lipid composition and the dynamic role of mitochondrial lipids in regulating bioenergetics, including ATP production, proton uncoupling, and mitochondrial electron leak. Finally, the authors propose a "bagpipe hypothesis" to explain the dynamic regulation of cristae architecture and bioenergetics by mitochondrial lipids.