Physiological functions of mitochondrial phospholipids. (A) Association of phospholipids and proteins in the IMM impacts stability of both protein complexes and membrane phospholipids. Loss of CL leads to RSC disassembly, while loss of OXPHOS proteins (thus disrupting RSC formation) results in faster CL turnover that is thought to elevate the MLCL/CL ratio. The amount of saturated CL also increases in the absence of OXPHOS complexes that induce CL remodeling. (B) CL-supported cristae structure via MICOS integrity. The mammalian MICOS complex is depicted. In the presence of CL, the MIC10 subcomplex, composed of MIC10, QIL1, MIC27, and MIC26, assembles and organizes cristae structure. MIC27 specifically interacts with CL. In the absence of CL, the MIC10 subcomplex is diffused, disrupting cristae morphology. MIC60 subcomplex assembly is independent of CL. (C) Phospholipid involvement in mitochondrial dynamics. (Top) DRP1 modulates membrane restriction in response to the local concentrations of CL and PA. DRP1 is recruited to the OMM and oligomerizes in a CL-dependent manner, leading to membrane constriction. It directly interacts with mitoPLD and binds mitoPLD-produced PA, which in turn suppresses division. (Bottom) MFN and MIGA promote OMM fusion where PA locally accumulates, as a consequence of MitoPLD-mediated CL hydrolysis. MIGA directly interacts with mitoPLD. OPA1 forms a dimer and induces IMM fusion at the CL-enriched sites.