The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein complexes of the respiratory chain. The cristae usually form tubular invaginations; however, triangular and vesicular cristae are observed in specific cell types.

The composition of the inner boundary membrane and cristae membrane differs significantly. Heterogeneity between the inner membrane domains and their specialized curved structure is important for respiratory functions. This compositional asymmetry is maintained by the tubular neck-like structure known as crista junctions that connect the inner boundary membrane and the cristae membrane. The cristae membrane has a small diameter of 20-40 nm and consequently has an extreme curvature. This distinct membrane structure is molded by several protein components, including the mitochondrial contact site and cristae organizing system (MICOS) and ATP synthase.

The MICOS is a conserved multi-protein complex that works with mitochondrial lipid cardiolipin, respiratory complexes, and additional factors. In addition to stabilizing the inner-membrane structure, MICOS plays multiple roles, including contact site formation between the inner and the outer membrane and promoting biosynthesis of specific proteins and polypeptides. Mutations in the MICOS subunits are linked to many human diseases such as Parkinson’s disease, hepatic-encephalopathy, and acute coronary conditions. In addition to MICOS, ATP synthase dimers that localize at the rims of cristae are crucial in the inner membrane morphology. Defective ATP synthase dimerization has been associated with Leigh’s syndrome, a neurometabolic disorder that progresses into acute respiratory failure.