Mitochondrial compartmentalization: emerging themes in structure and function

Mitochondria contain two membranes that partition the organelles into compositionally and functionally distinct subcompartments that are defined by a topologically complex ultrastructure. In addition to their morphological complexity, mitochondria are pleomorphic, undergoing morphogenesis events with an extent and frequency that is only now becoming fully appreciated. The protein complexes that define inner membrane morphology form an interactive network with lipid interactions, and new insights are illuminating how they establish and regulate compartmentalization. The general determinants of compartmentalization, as well as the factors that govern protein and lipid distribution, have recently been identified. Novel research on the functional relevance of compartmentalization has highlighted a key role of regulated cristae subcompartment structure in bioenergetics and in human diseases. Within cellular structures, compartmentalization is the concept of spatial segregation of macromolecules, metabolites, and biochemical pathways. Therefore, this concept bridges organellar structure and function. Mitochondria are morphologically complex, partitioned into several subcompartments by a topologically elaborate two-membrane system. They are also dynamically polymorphic, undergoing morphogenesis events with an extent and frequency that is only now being appreciated. Thus, mitochondrial compartmentalization is something that must be considered both spatially and temporally. Here, we review new developments in how mitochondrial structure is established and regulated, the factors that underpin the distribution of lipids and proteins, and how they spatially demarcate locations of myriad mitochondrial processes. Consistent with its pre-eminence, disturbed mitochondrial compartmentalization contributes to the dysfunction associated with heritable and aging-related diseases. Within cellular structures, compartmentalization is the concept of spatial segregation of macromolecules, metabolites, and biochemical pathways. Therefore, this concept bridges organellar structure and function. Mitochondria are morphologically complex, partitioned into several subcompartments by a topologically elaborate two-membrane system. They are also dynamically polymorphic, undergoing morphogenesis events with an extent and frequency that is only now being appreciated. Thus, mitochondrial compartmentalization is something that must be considered both spatially and temporally. Here, we review new developments in how mitochondrial structure is established and regulated, the factors that underpin the distribution of lipids and proteins, and how they spatially demarcate locations of myriad mitochondrial processes. Consistent with its pre-eminence, disturbed mitochondrial compartmentalization contributes to the dysfunction associated with heritable and aging-related diseases. crescent-shaped domain that interacts with curved membrane surfaces to both promote and detect local membrane curvatures, named after the BIN/Amphiphysin/Rvs proteins in which they are found. attribute of a semipermeable barrier that allows the selective flux of ions down their electrochemical gradients, typically energetically coupled to another process. difference in proton electrochemical potential (Δμ~H+). The potential across the CM of actively respiring mitochondria has a major contribution from the electric potential (ΔΨm ~150 mV, matrix negative) and a minor contribution from the proton concentration difference (ΔpH ~1 unit, matrix alkaline). ABC transporters that utilize the energy provided by ATP hydrolysis to move specific phospholipids against their gradient from the outer to the inner leaflet (flippase) or from the inner to the outer leaflet (floppase). Together, they help generate lipid asymmetry in membranes. a network of physically interacting molecules defining a specific biochemical function or process. controlled process of cell death initiated by proapoptotic effectors (e.g., Bax/Bak) that interact with mitochondria to release factors (e.g., cyt c) that propagate a proteolytic cascade. regions of close apposition between two membranes, generally comprising interacting protein complexes, that facilitate signaling and the passage of small molecules. Such sites can be interorganellar, mediating connections that are homotypic (between the same organelles) or heterotypic (between different organelles). They can also exist between membranes of a single organelle. physical bending of a biomembrane to produce positively (convex) and negatively (concave) curved surfaces. displaying plasticity in structure and size. Ca2+-dependent transporters that equilibrate phospholipids between membrane leaflets. Unlike flippases and floppases, scramblases do not need an external energy source to transport lipids. protein family named after primary members (stomatin, prohibitin, flotillin, and HflK/C), which commonly associate on membranes to form lipid raft microdomains that recruit specific protein complexes. assembly of the respiratory complexes (CI, CIII, and CIV) into supramolecular structures. This solid-state arrangement likely enhances metabolic efficiency compared with a fluid-state model in which individual complexes are connected by freely diffusing electron carriers. the structure of cellular or subcellular objects that requires higher magnification than standard optical microscopy, typically observable by EM or super-resolution microscopy.