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Cavellini, L.

Publications and source records attributed to Cavellini, L..

2 recordsLinked to original sources

A constricted mitochondrial morphology optimizes respiration.

Mitochondria assemble in a dynamic tubular network with a morphology governed by mitochondrial fusion and fission, which regulate all mitochondrial functions including oxidative phosphorylation 1-4. Yet, the link between mitochondrial morphology and respiration remains unclear 5-9. Here, we discover a previously unknown mitochondrial morphology dedicated to respiratory growth of Saccharomyces cerevisiae, which we refer to as "Ringo". The Ringo morphology is characterized by stable constrictions of mitochondrial tubules. Ringo constrictions are mediated by the yeast dynamin Dnm1 and, unlike mitochondrial fission 10-12, occur in the absence of contacts with the endoplasmic reticulum. Our data show that the Ringo morphology regulates mitochondrial DNA homeostasis during respiration to ensure stoichiometric assembly of OXPHOS complexes, demonstrating that the shape of mitochondria actively contributes to optimal respiration. One-Sentence Summary: We report a new mitochondrial morphology that actively contributes to optimal respiration in yeast.

cell biology↗

Lys716 in the transmembrane domain of yeast mitofusin Fzo1 modulates anchoring and fusion

Outer mitochondrial membrane (OMM) fusion is an important process for the cell and organism survival, as its dysfunction is linked to neurodegenerative diseases and cancer. The OMM fusion is mediated by members of the dynamin-related protein (DRP) family, named mitofusins. The exact mechanism by which the mitofusins contribute to these diseases, as well as the exact molecular fusion mechanism mediated by mitofusin, remains elusive. We have performed extensive multiscale molecular dynamics simulations using both coarse-grained and all-atom approaches to predict the dimerization of two transmembrane domain (TM) helices of the yeast mitofusin Fzo1. We identify specific residues, such as Lys716, that can modulate dimer stability. Comparison with a previous computational model reveals remarkable differences in helix crossing angles and interfacial contacts. Overall, however, the TM1-TM2 interface appears to be stable in the Martini and CHARMM force fields. Replica-exchange simulations further tune a detailed atomistic model, as confirmed by a remarkable agreement with an independent prediction of the Fzo1-Ugo1 complex by AlphaFold2. Functional implications, including a possible role of Lys716 that could affect membrane interactions during fusion, are suggested and consistent with experiments monitoring mitochondrial respiration of selected Fzo1 mutants.

bioinformatics↗