Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis.

Ruchika Anand,Andreas S Reichert,Arun Kumar Kondadi

doi:10.3390/biology10070600

Ruchika Anand, Andreas S Reichert + Show 1 more

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https://doi.org/10.3390/biology10070600

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Abstract

Simple SummaryMitochondria 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.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 F1FO 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.

Highlights

The Organization of the Mitochondrial Inner Membrane Mitochondria are important organelles that perform vital functions including energy conversion, cellular metabolism, apoptosis, calcium buffering and iron–sulfur cluster biogenesis
The mitochondrial contact site and cristae organizing system’ (MICOS) complex is important for maintaining the cristae and crista junctions (CJs) architecture and mediates contact sites between the inner membrane (IM) and outer membrane (OM). It is overall highly conserved [22,23] and composed of seven subunits including MIC10/Minos1, MIC26/APOO, MIC27/APOOL, MIC13/QIL1, MIC19/CHCHD3, MIC25/CHCHD6 and MIC60/IMMT (Figure 1). It is largely enriched at CJs, and the deletion of subunits of the MICOS complex causes loss of CJs, leading to aberrant cristae structures that are detached from the inner boundary membrane (IBM), resulting in the formation of stacks or concentric circles in the matrix [17,18,19,20,21]
Several new findings have revealed that cristae are highly dynamic entities and that a central role regulating this can be attributed to the MICOS complex

Summary

Introduction

The Organization of the Mitochondrial Inner Membrane Mitochondria are important organelles that perform vital functions including energy conversion, cellular metabolism, apoptosis, calcium buffering and iron–sulfur cluster biogenesis. The hallmark feature of double membrane-enclosed mitochondria is the invaginations of the inner membrane (IM) into the matrix termed cristae. The rest of the IM that runs parallel to the outer membrane (OM) is termed the inner boundary membrane (IBM), which is compositionally and functionally distinct from the cristae membrane (CM) [1,2]. The CM and IBM are connected by small pore-like openings termed crista junctions (CJs) [3]. CJs restrict the entry of metabolites into the lumen of cristae due to their small diameter of 12–40 nm and potentially regulate many mitochondrial functions [4]. The ultrastructural features of cristae and CJs were described long ago [13], the fundamental question of how they are formed is not yet fully understood. The dynamin-like GTPase OPA1, the F1FO ATP synthase complex and the MICOS complex are the three main known mediators of cristae formation far (Figure 1) [16]

The MICOS Complex Plays a Primary Role in IM Organization

Other Important Molecular Players Playing Vital Roles in IM Organization

MICOS Complex Regulates Apparent Cristae Fusion and Fission Cycles

Possible Implications of Cristae Dynamics

Findings

Conclusions