Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis

SIMPLE SUMMARY: Mitochondria possess an outer and inner membrane. The part of the inner membrane parallel to the outer membrane is termed the inner boundary membrane, while the cristae membrane folds towards the mitochondrial matrix and houses the respiratory chain complexes. Crista junctions are located at the interface of the inner boundary membrane and the cristae membrane and contain the important ‘mitochondrial contact site and cristae organizing system’ complex. Despite the growing evidence that the mitochondrial inner membrane could remodel, cristae membranes were largely considered static for nearly seventy years, as the observations were mostly based on electron microscopy and tomography. Recently, using fluorescence super-resolution techniques, several studies showed that cristae membranes undergo dynamic remodeling in living cells, and probably even fission and fusion of the inner membrane. In this review, we discuss the important recent literature conveying the emerging role of the MICOS complex in cristae dynamics and its relation to cristae biogenesis. As the aberrant inner membrane architecture is connected to various pathologies such as cardiomyopathies, neurodegeneration and diabetes, understanding the roles of various molecules connected with cristae biogenesis and dynamics would shed light on the pathophysiology, probably leading to therapeutics in the near future. ABSTRACT: Mitochondria are double membrane-enclosed organelles performing important cellular and metabolic functions such as ATP generation, heme biogenesis, apoptosis, ROS production and calcium buffering. The mitochondrial inner membrane (IM) is folded into cristae membranes (CMs) of variable shapes using molecular players including the ‘mitochondrial contact site and cristae organizing system’ (MICOS) complex, the dynamin-like GTPase OPA1, the F(1)F(O) ATP synthase and cardiolipin. Aberrant cristae structures are associated with different disorders such as diabetes, neurodegeneration, cancer and hepato-encephalopathy. In this review, we provide an updated view on cristae biogenesis by focusing on novel roles of the MICOS complex in cristae dynamics and shaping of cristae. For over seven decades, cristae were considered as static structures. It was recently shown that cristae constantly undergo rapid dynamic remodeling events. Several studies have re-oriented our perception on the dynamic internal ambience of mitochondrial compartments. In addition, we discuss the recent literature which sheds light on the still poorly understood aspect of cristae biogenesis, focusing on the role of MICOS and its subunits. Overall, we provide an integrated and updated view on the relation between the biogenesis of cristae and the novel aspect of cristae dynamics.