Trends in Biochemical Sciences
ReviewSpecial Issue: Mitochondria & MetabolismMitochondrial Cristae: Where Beauty Meets Functionality
Section snippets
The Dynamic Functional Form of Mitochondria
‘Form ever follows function’ is a famous quote from the American architect Louis Sullivan. He reached this conclusion by observing nature, where function is determined by specific and defined structures. Mitochondria are an extraordinary example of this axiom: they are dynamic organelles that have crucial roles in many cellular processes, including apoptosis, metabolism, reactive oxygen species (ROS) detoxification, and ATP production through OXPHOS. Such a variety of functions is coupled to a
Mitochondrial Cristae: Dynamic Biochemical Reactors
Mitochondria reorganize their internal structure by modifying the shape of the cristae. Nearly 50 years ago, Hackenbrock noted that, in response to low ADP concentrations, the inner membrane morphology changed from a ‘condensed’ state, characterized by a contracted and dense matrix compartment and wide cristae, to an ‘orthodox’ state, with an expanded, less dense matrix and a more compact cristae compartment [8]. However, these pioneering observations remained confined to the aficionados of
Cristae and OXPHOS: An Intimate Liaison
Cristae are the site of OXPHOS: 94% of complex III and ATP synthase [17] and approximately 85% of total cytochrome c are stored in this compartment [9] (Box 2). Evolutionarily, there is a molecular correlation between the core cristae-shaping machinery, the emergence of cristae, and the OXPHOS system [18], further supporting the concept that cristae are the true bioenergetic membrane of the mitochondrion. The OXPHOS system comprises four different complexes that are further assembled into
Mitochondrial-Shaping Proteins: Masterminds of OXPHOS Organization
The mitochondrial-shaping proteins are a family of proteins that orchestrate mitochondrial morphology and dynamics. The family includes a group of GTP-dependent dynamin-like proteins involved in the fusion and fission cycle of mitochondria, including the profusion proteins Optic atrophy 1 (OPA1) and Mitofusin 1,2, and the profission Drp1, as well as structural proteins, such as the mitochondrial contact site and cristae-organizing system (MICOS) complex or the Prohibitin (PHB) family proteins
Cristae Structure versus ATP Synthase Dimerization: What Comes First?
The plethora of evidence discussed here provides strong evidence for cristae shape as a key factor for the assembly of OXPHOS complexes. Nevertheless, in yeast especially, the dimerization of ATP synthase has been deemed necessary to shape mitochondrial cristae. Deletion of subunits e and g of ATP synthase in yeast and in human cell lines abolished the dimerization of ATP synthase and caused changes to the cristae membrane 64, 65. Moreover, ρ0 cells, which lack the subunit F0 and only have F1
Signaling Pathways Modulating Cristae Morphology
Mitochondria are able to change their morphology to match with the needs of the cells (reviewed in [76]). In turn, mitochondria are sensors of cellular metabolism that can trigger specific gene expressions or modulate different cellular pathways (reviewed in [26]). There is an extensive literature covering the pathways of fusion and fission. We know that these events are tuned by the fine coordination of post-translational modification. For example, Mitofusin 2 is ubiquitinated by the E3
Concluding Remarks
While earlier observations correlated changes in cristae shape with mitochondrial respiration, the availability of molecular tools to manipulate mitochondrial ultrastructure resulted in a leap forward in our understanding of how form and function are connected in mitochondria. It is now clear that cristae shape affects the performance of the electron transport chain, and complexes and supercomplexes formation and dynamics, and is ultimately important for metabolic adaptation (Figure 1).
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