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Why do mitochondria look the way they do?

Why do mitochondria look the way they do?
Credit: Wikipedia commons

One of the biggest challenges in biology today is to explain the structure of the cristae, the inner membranes of mitochondria. An explanation in this case is a set of principles for predicting what form cristae will take after basic metabolic manipulations of the environment in which the mitochondria are located. These principles will therefore be a description of the true function of mitochondria, something that has so far hardly imagined sig.

Recent advances in techniques such as supercomponent light cell light microscopy and electron tomography have provided new insights into cristae's dynamic behavior. A detailed architecture of entire mitochondrial volume can now be constructed from a series of tilt images projected back to create 3D tomograms. On Monday, we discussed how cristae are transformed and reconfigured according to the abundance and health of several inner membrane and matrix proteins. The pretext for that analysis was the structural and biochemical similarities between membranes in mitochondria, thylakoids and myelin, which presumably help to channel metabolites in the production of energy.

In a recent article from The Royal Society's Open biology, researchers explain the biogenesis of cristae through the coordinated activities of four major evolutionarily conserved pathways, from protists and yeasts up to higher eukaryotes like ourselves: dimer formation and oligomerization of ATP synthase at the cristae edges, assembly of it ' mitochondrial contact site 'and cristae organizing system' (MICOS) by crista junctions, membrane remodeling of an inner membrane-associated, dynamine-related GTPase (Mgm1 in yeast and OPA1 in mammals) and proper adjustment of the membrane lipid composition.

For the first pathway involving ATP synthesis, several things are clear. As we reported earlier, the spontaneous dimerization of ATP synthase dictates at precisely defined and species-dependent angles in ordered rows the geometry of the ground floor. In contrast to respiratory complexes I-IV, which are assembled on the flat inner boundary membrane, ATP synthase (complex V) is fully assembled deep in the cristae membranes. While several ATP synthase subunit proteins are required for proper cristae formation, the Atp20 and Atp21 subunits are strictly necessary.

An excess of ADP induces a condensed conformation with large, swollen intra-crystalline spaces. In contrast, under ADP-limiting conditions, mitochondria adopt the orthodox conformation with contracted intra-crystal space. In the giant amoeba Chaos carolinensis, mitochondria usually contain randomly oriented tubular cristae. With starvation, enlarged cristae assume a cubic morphology with a zigzag-like pattern. In mice, apoptotic agents cause fusion of individual cristae with subsequent release of cytochrome c from the intra-crystalline space into the border region.

Hvorfor ser mitokondrier ud som de gør?

For the second way, the collection of MICOS contact points, research has established that critical proteins, such as those from the MIC60-related gene family, are present as far back as mitochondrial endosymbiotic ancestors - the α-proteobacterium. Many of these former mitochondrial carriers show already differentiated intracytoplasmic membrane structures. Inevitably, species that have simplified their mitochondria to the point that cristae are absent are missing, corresponding to the MICOS-related genes. Gene expression of MIC60 homologs in Δmic60 yeast mutants rescues the ultrastructural mitochondrial defects.

The third pathway includes the dynamamine-related GTPases, which coordinate the fusion and fission of both inner and outer membranes. Upon fission, these proteins polymerize into contractile rings that use contractile forces to clamp mitochondria. The result is now understood to be dependent on interactions between these proteins, both with the MICOS complex and the cristae compounds, and also the internal and external membrane transport systems assembled there. These include the TIM and TOM membrane translocator complexes.

The fourth pathway includes the phospholipids of the mitochondrial membrane itself. Mitochondria house the cardiolipin biosynthetic pathway and are also involved in the synthesis of phosphatidylethanolamine. Along with phosphatidylcholine, these are the three major phospholipids mitochondria work with. Most of the building blocks of mitochondrial lipids are synthesized in the ER and therefore need to be imported by mechanisms involving close apposition to the ER. Once inside the outer membrane, the distribution of lipids is mediated by intermembrane space-localized transport proteins from the Ups / PRELI family,

Mitochondria do not create geometry from scratch, but utilize and build on the natural physical forms that occur spontaneously in lipids. Left to their own entity, lipids form concentric lamella structures, which can then be expanded and amplified by specific proteins. Fine-scale measurements have now revealed that individual cristae are functionally independent and may have significantly different membrane potentials.

Cristae formation involves a closely related interplay between the above four shaping influences. For example, the activities of the MICOS complex and ATP synthase dimerization are both cooperative and antagonistic. MICOS induces negative membrane curvature, while ATP synthase induces positive curvature at cristae tips and edges. New computational models, which are currently being developed in laboratories around the world, where the ratio of these different components can be fine-tuned and adjusted, will greatly help define what controls the shape of mitochondria.

Unexpected insight into the dynamic structure of mitochondria

More information: Till Klecker et al, Pathways forming the mitochondrial inner membrane, Open biology (2021). DOI: 10.1098 / rsob.210238

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Citation: Why do mitochondria look the way they do? (2022, January 19) retrieved January 19, 2022 from

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