Structural and mechanistic investigation on mitochondrial fusion - Archive ouverte HAL Access content directly
Journal Articles Biochimica biophysica acta (BBA) - Bioenergetics Year : 2022

Structural and mechanistic investigation on mitochondrial fusion


Mitochondria are key organelles that change their size, shape and morphology undergoing a series of fusion and fission events, referred as mitochondrial dynamics. Pivotal components mediating the fusion and fission process of the outer/inner membrane(s) belong to the dynamin family of GTPases named DRPs. While the ability of DRPs to mediate membrane fission is well documented, the mechanism of outer-membrane Fusion DRPs, named mitofusins are poorly understood. Recently this deadlock was partially circumvented with solving the truncated structures of human mitofusins MFN1 and MFN2 [1], [2]. The crystallographic structure of these mini-MFNs revealed that its fold is strikingly similar to that of the corresponding portion of BDLP, the Bacterial Dynamin Like Protein from the cyanobacteria Nostoc punctiforme [3]. GTP binding by BDLP results in a switch from a compact structure to an ‘open’ conformation that stimulates its oligomerization and promotes its ability to shape the morphology of lipid membranes [3]. It is thus likely that mitofusins undergo similar conformational rearrangements. Our group have recently demonstrated the importance of the N terminal residues 60 to 100, which are neither conserved in BDLP nor MFNs, in yeast mitofusin function [4]. Hence, structural analysis of the fragments containing these residues is pivotal to understand the role of Fzo1. Herein, we will report our effort to successfully purify and crystallize a truncated form of Fzo1. This will provide fundamental insights into how Fzo1 mediates yeast mitochondrial fusion and it will allow us to further investigate the role of the residues 60 to 100. [1] Y.-L. Cao et al., MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion, Nature, vol. 542 (2017) 372–376. [2] Y.-J. Li et al., Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset, Nat. Commun., 10 (2019) 4914. [3] H. H. Low, J. Löwe, A bacterial dynamin-like protein, Nature, 444 (2006) 766–769. [4] D. De Vecchis, L. Cavellini, M. Baaden, J. Hénin, M. M. Cohen, A. Taly, A membrane-inserted structural model of the yeast mitofusin Fzo1, Sci. Rep., 7 (2017) 10217.
Not file

Dates and versions

hal-03963810 , version 1 (10-02-2023)



Mohammad Ozeir, Laetitia Cavellini, Julien Henri, Mickael Cohen. Structural and mechanistic investigation on mitochondrial fusion. Biochimica biophysica acta (BBA) - Bioenergetics, 2022, 1863, pp.148800. ⟨10.1016/j.bbabio.2022.148800⟩. ⟨hal-03963810⟩
5 View
0 Download



Gmail Facebook Twitter LinkedIn More