The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data...

Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy wi...

The mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) dynamically regulate mitochondrial membrane architecture. Through systematic proteomic analysis of human MICOS, we identified QIL1 (C19orf70) as a novel conserved MICOS subunit. QIL1 depletion disrupted CJ structure in cultured human cells and in Drosophila muscle and neuronal cells in vivo. In human cells, mitoc...

The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis. Whether and how they physically and functionally interact is unclear. Here, we provide evidence that OPA1 is epistatic to MICOS in the regulation of cristae shape. Proteomic analysis identifies multiple MICOS components in na...

The function of mitochondria depends on the proper organization of mitochondrial membranes. The morphology of the inner membrane is regulated by the recently identified mitochondrial contact site and crista organizing system (MICOS) complex. MICOS mutants exhibit alterations in crista formation, leading to mitochondrial dysfunction. However, the mechanisms that underlie MICOS regulation remain ...

The inner boundary and the cristae membrane are connected by pore-like structures termed crista junctions (CJs). The MICOS complex is required for CJ formation and enriched at CJs. Here, we address the roles of the MICOS subunits Mic27 and Mic10. We observe a positive genetic interaction between Mic27 and Mic60 and deletion of Mic27 results in impaired formation of CJs and altered cristae membr...

Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane s...

Mitochondria are organelles with a complex architecture. They are bounded by an envelope consisting of the outer membrane and the inner boundary membrane (IBM). Narrow crista junctions (CJs) link the IBM to the cristae. OMs and IBMs are firmly connected by contact sites (CS). The molecular nature of the CS remained unknown. Using quantitative high-resolution mass spectrometry we identified a no...

The MItochondrial Contact Site and Cristae Organizing System (MICOS) is required for the biogenesis and maintenance of mitochondrial cristae as well as the proper tethering of the mitochondrial inner and outer membranes. We recently demonstrated that the core components of MICOS, Mic10 and Mic60, are near-ubiquitous eukaryotic features inferred to have been present in the last eukaryote common ...

Mitochondria are eukaryotic organelles that originated from an endosymbiotic α-proteobacterium. As an adaptation to maximize ATP production through oxidative phosphorylation, mitochondria contain inner membrane invaginations called cristae. Recent work has characterized a multi-protein complex in yeast and animal mitochondria called MICOS (mitochondrial contact site and cristae organizing syste...